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Multiple metabolic and biochemical interrelationships, as well as the most recent views on mechanisms of malignant cell growth, proliferation, and oncogen activity mediated by the Na+/H+ antiporter, can be integrated from the unitarian point of view of the dynamics of the hydrogen ion to parallel pH-related mechanisms involved in the Spontaneous Regression (SR) of some malignant tumors. Also, pH-related growth inhibitors of the amiloride series are considered as possible agents to be used in the adjuvant and co-adjuvant treatment of some human tumors as well as in the control of the metastatic process and in overcoming cancer multidrug resistance (MDR).

A case is presented in which the minor strut of a Bjork-Shiley mitral prosthesis fractured 11 years postoperatively. The relevant diagnostic contributions of transthoracic and transesophageal echocardiography are discussed.

La ecocardiografia es una tecnica utilizada de rutina en la evaluacion de la funcion cardiaca. La definicion de los bordes endocardicos es fundamental para valorar de forma correcta la contractilidad global y segmentaria del ventriculo izquierdo. En algunas ocasiones esto resulta dificil debido a la inadecuada ventana acustica de los pacientes. Las nuevas tecnicas ecocardiograficas podrian ayudar a diagnosticar de forma precisa e incruenta determinadas enfermedades que pasaban inadvertidas con las tecnicas tradicionales. Presentamos el caso de un paciente diagnosticado en el ecocardiograma basal de alteraciones en la contractilidad segmentaria, tipo hipocinesia lateral y apical, en el que la utilizacion de la imagen armonica con ecocardiografia de contraste permitio cambiar el diagnostico inicial. El paciente presentaba realmente una miocardiopatia hipertrofica severa con obstruccion mesoventricular, sin alteraciones segmentarias de la contractilidad.

Different research groups have recently described a proton [H(+)]-related mechanism underlying the initiation and progression of the neoplastic process in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (pH(i) to pH(e)) as compared to normal tissue pH gradients. This basic specific abnormality of the relationship between the intracellular and the extracellular proton dynamics, a phenomenon that is increasingly considered to be one of the most differential hallmarks of cancer, has led to the formation of a unifying thermodynamic view of cancer research that embraces cancer fields from etiopathogenesis, cancer cell metabolism, multiple drug resistance (MDR), neovascularization and the metastatatic process to selective apoptosis, cancer chemotherapy and even the spontaneous regression of cancer (SRC). This reversed proton gradient is driven by a series of proton export mechanisms that underlie the initiation and progression of the neoplastic process. This means that therapeutic targeting of the transporters that are active in cancer cells could be selective for malignancy and is likely to open new pathways towards the development of more effective and less toxic therapeutic measures for all malignant diseases. Here we review the transporters involved in driving the reversed proton gradient and their specific inhibitors.

Salvador Harguindey1, Gorka Orive2,6, Ramón Cacabelos3, Enrique Meléndez Hevia4, Ramón Díaz de Otazu5, et al1Institute of Clinical Biology and Metabolism, Vitoria, Spain; 2Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of The Basque Country, Vitoria, Spain; 3Department of Clinical Neuroscience, EuroEspes Biomedical Research Center, Bergondo, La Coruña, Spain; 4Institute for Cellular Metabolism, Tenerife, Spain; 5Department of Pathology, Hospital Txagorritxu, Vitoria, Spain; 6Biotechnology Institute (BTI), Vitoria, SpainAbstract: A novel and integral approach to the understanding of human neurodegenerative diseases (HNDDs) and cancer based upon the disruption of the intracellular dynamics of the hydrogen ion (H+) and its physiopathology, is advanced. From an etiopathological perspective, the activity and/or deficiency of different growth factors (GFs) in these pathologies are studied, and their relationships to intracellular acid-base homeostasis reviewed. Growth and trophic factor withdrawal in HNDDs indicate the need to further investigate the potential utilization of certain GFs in the treatment of Alzheimer disease and other neurodegenerative diseases. Platelet abnormalities and the therapeutic potential of platelet-derived growth factors in these pathologies, either through platelet transfusions or other clinical methods, are considered. Finally, the etiopathogenic mechanisms of apoptosis and antiapoptosis in HNDDs and cancer are viewed as opposite biochemical and biological disorders of cellular acid-base balance and their secondary effects on intracellular signaling pathways and aberrant cell metabolism are considered in the light of the both the seminal and most recent data available. The “trophic factor withdrawal syndrome” is described for the first time in English-speaking medical literature, as well as a Darwinian-like interpretation of cellular behavior related to specific and nonspecific aspects of cell biology.Keywords: neurodegenerative diseases and growth factors; Alzheimer’s Disease, human neurodegenerative diseases, cancer, intracellular acid-base homeostasis, apoptosis, antiapoptosis, etiopathogenesis and treatment

En aquest treball final de carrera s'ha realitzat una aplicació per a simulacions de granges porcines amb dues interfícies, una web i una d'escriptori. Les tecnologies emprades han estat el llenguatge de programació Java i les bases de dades MySQL; així com les diferents llibreries (JfreeChart...) necessàries per a les diferents funcionalitats de l'aplicació.

Abnormalities in the intricate intracellular signalling pathways play a key role in the deregulation of either spontaneous (normal or pathological) or induced (therapeutic) cell death mechanisms. Some of these pathways are increasingly becoming molecular therapeutic targets in different processes, ranging from neurodegenerative diseases to cancer. Recent discoveries in research and treatment have shown that failure to induce selective cell apoptosis in hyperproliferative processes, like neoplastic diseases, and the failure to prevent spontaneous cell death in neurodegenerative diseases (HNDDs) such as Alzheimer's disease (AD), multiple sclerosis (MS), amyothrophic lateral sclerosis (ALS), Huntington's disease (HD), and retinitis pigmentosa (RP), can be interpreted as problems stemming from the same basic mechanisms but moving in diametrically opposed directions. The integrated approach advanced here represents an interdisciplinary attempt to stimulate an integrated vision of two otherwise widely separated areas of research, experimental neurology and oncology. This kind of approach to the prevention of apoptosis (therapeutic antiapoptosis) and/or other forms of cell death in HNNDs, as well as to resistance to therapeutic apoptosis in cancer (pathological antiapoptosis), has the scope to improve the understanding of the dualistic nature of the basic abnormalities underlying the pathological deregulation of cell death. In this context, an intracellular pH (pH(i))-related approach to these opposed situations is advanced to provide a unified theory of the apoptosis-antiapoptosis machinery. Some potential therapeutic possibilities opened by these lines of research, regarding the utilization of human growth factors and/or cellular anti-acidification measures directed to sustain cellular acid-base homeostasis in different HNNDs are considered because of their potential therapeutic benefit. Finally, we advance some possible dangers and side-effects raised by these very same treatment efforts.

Perioperative cardiovascular complications are a significant cause of post-surgical morbidity and mortality in patients undergoing major vascular surgery (MVS). Dobutamine stress echocardiography is the most important method of detecting coronary artery disease in these patients. Although dipyridamole stress echocardiography (SE-DIP) and dobutamine stress echo (SE-DOB) have demonstrated similar negative predictive value (NPV) in the early postoperative period in patients undergoing MVS, there are few data concerning the negative predictive value of SE-DIP in the long-term follow-up of this subgroup of patients.Our aim was to compare the long-term NPV of these two types of stress echocardiography and to compare it with perioperative NPV, based on the working assumption that they are similar.A retrospective study was made of 157 patients based on preoperative evaluations for vascular surgery between February 1997 and February 2000. Clinical history and the results of consecutive stress exams were analyzed. We excluded patients with a positive stress echo and those that performed dobutamine stress echo which was considered inconclusive since they did not reach 85% of the maximum heart rate for their age. Therefore, 110 patients were included, 29 (26.4%) with dobutamine and 81 (73.6%) dipyridamole-atropine. The patients were followed after surgery for a period of 2.2 +/- 1 years. Cardiac events were defined as cardiac death, nonfatal acute myocardial infarction and hospitalization for unstable angina. The cumulative probability of event-free survival was compared.The patients' mean age was 65 +/- 10 years, and 108 (98.1%) were men. After 2.2 +/- 1 years of follow-up, 7 cardiac events occurred in the group with negative SE-DIP (8.6%) and 3 in patients with negative SE-DOB (10.3%). There were no statistically significant differences between the two groups concerning event-free survival (3.7 +/- 0.2 vs. 3.5 +/- 0.2 years for SE-DIP and SE-DOB respectively; p = 0.91). Negative predictive values for SE for perioperative and long-term cardiac events were 97.3% and 90.9% respectively.SE-DIP is a good alternative to SE-DOB in the preoperative evaluation of patients undergoing MVS, with the NPV of SE-DIP being similar to SE-DOB in the perioperative period and in long-term follow-up.

Looked at from the genetic point-of-view cancer represents a daunting and, frankly, confusing multiplicity of diseases (at least 100) that require an equally large variety of therapeutic strategies and substances designed to treat the particular tumor. However, when analyzed phenotypically cancer is a relatively uniform disease of very conserved 'hallmark' behaviors across the entire spectrum of tissue and genetic differences [D. Hanahan, R.A. Weinberg, Hallmarks of cancer, Cell 100 (2000) 57-70]. This suggests that cancers do, indeed, share common biochemical and physiological characteristics that are independent of the varied genetic backgrounds, and that there may be a common mechanism underlying both the neoplastic transformation/progression side and the antineoplastic/therapy side of oncology. The challenge of modern oncology is to integrate all the diverse experimental data to create a physiological/metabolic/energetic paradigm that can unite our thinking in order to understand how both neoplastic progression and therapies function. This reductionist view gives the hope that, as in chemistry and physics, it will possible to identify common underlying driving forces that define a tumor and will permit, for the first time, the actual calculated manipulation of their state. That is, a rational therapeutic design. In the present review, we present evidence, obtained from a great number of studies, for a fundamental, underlying mechanism involved in the initiation and evolution of the neoplastic process. There is an ever growing body of evidence that all the important neoplastic phenotypes are driven by an alkalization of the transformed cell, a process which seems specific for transformed cells since the same alkalinization has no effect in cells that have not been transformed. Seen in that light, different fields of cancer research, from etiopathogenesis, cancer cell metabolism and neovascularization, to multiple drug resistance (MDR), selective apoptosis, modern cancer chemotherapy and the spontaneous regression of cancer (SRC) all appear to have in common a pivotal characteristic, the aberrant regulation of hydrogen ion dynamics [S. Harguindey, J.L. Pedraz, R. Garcia Canero, J. Perez de Diego, E.J. Cragoe Jr., Hydrogen ion-dependent oncogenesis and parallel new avenues to cancer prevention and treatment using a H+-mediated unifying approach: pH-related and pH-unrelated mechanisms, Crit. Rev. Oncog. 6 (1) (1995) 1-33]. Cancer cells have an acid-base disturbance that is completely different than observed in normal tissues and that increases in correspondence with increasing neoplastic state: an interstitial acid microenvironment linked to an intracellular alkalosis.

Los intricados caminos de señalización intracelular en la desregulación de la apoptosis, espontánea o inducida, se han convertido en las principales dianas terapéuticas en enfermedades que van desde las neoplásicas a los procesos neurodegenerotivos. A la vista de los tendencias actuales en investigación se puede afirmar que el fracaso en inducir una apoptosis selectiva en las células y tumores cancerosas (proapoptosis), y en sentido contrario, lo imposibilidad de evitar lo apoptosis espontánea en enfermedades neurodegenerativas como el Alzheimer (antiapoptosis), representan una raíz y árbol común pora dos ramas, o áreas de la medicina, creciendo en sentidos opuestos. El enfoque aquí presentado es un intento de estimular una visión integrada de ambas ramas y áreas de investigación, oncología y neurología, en orden a mejorar la comprensión de sus naturalezas íntimas, tratando así de incrementar el entendimiento de las anormalidades básicas y clínicas de los procesos bajo estudio. A esto se puede acceder a través de un escalonamiento diferenciador de las posibilidades terapéuticas que se están abriendo en la actualidad así como merced o una consideración preliminar de los peligros potenciales que pueden surgir en el empeño. The intricated pathways of intracellular signaling and the deregulation of cell apoptosis, either spontaneous or induced, are becoming the main molecular and therapeutic targets ranging from cancer to neurodegenerative diseases. Modern trends in research and treatment show that the failure to induce selective cancer cell and tamor apoptosis (proapoptosis), and, in the opposite direction, the failure to prevent the spontaneous apoptosis of neurodegenerative diseases, like Alzheimer's disease, can be interpreted as problems representing two branches, or areas, of medicine growing in an opposite direction. The approach here advanced represents an attempt to stimulate an integral vision of both branches or areas of research, oncology and neurology, hoping to improve the understanding of the intimate nature of the basic and clinical abnormalities under investigation. A stop by step differentiation of the therapeutic possibilities that are being opened nowadays is considered, as well as some preliminary and potential dangers raised by the very same treatment efforts.

Acute dissection of the aorta is a life-threatening condition requiring immediate diagnosis and definitive treatment. Transoesophageal echocardiography may be considered the diagnostic procedure of choice in the assessment of patients with aortic dissection. A detailed morphological and functional study of the aorta must be obtained quickly. This report summarizes the echo-anatomical correlation of two distinct echocardiographic images of patients with aortic dissection.

Background: Dobutamine echocardiography (DSE), positron emission tomography (PET) and 201Tl-single photon emission computed tomography (SPECT) have been used to identify myocardial viability. There are few reports, however, that compare high doses DSE with myocardial metabolic and perfusion imaging techniques in the same patient population. The aim of this study was to determine the correlation between high doses DSE, metabolic PET and 201Tl-SPECT imaging to predict the recovery of function after revascularization in patients with severe left ventricular (LV) dysfunction. Methods: Twenty-five patients underwent DSE (up to 40 μg/kg/min), rest and 4-hour redistribution 201Tl SPECT, rest 13N-ammonia and 18fluoro-deoxy-glucose PET imaging and coronary angiography 7–10 days before surgical revascularization. A follow-up 2D-echocardiography was performed 6 weeks after surgery. Results: Of the 109 successfully revascularized segments with severe dysfunction, 62(57%) improved. LV ejection fraction increased from 30 ± 10% to 42 ± 13 at follow-up (p < 0.05). 201Tl SPECT, PET and the presence of contractile reserve determined by DSE had a similar sensitivity (77–87%) to predict recovery of function, but specificity was higher for the PET mismatch pattern and biphasic DSE (85–89%) than for any of the 201Tl viability patterns (19–64%). The highest positive predictive values were obtained by biphasic DSE and PET mismatch pattern (78–79%) compared to all other criteria (54–67%). In a multivariate model, which included evidence of viability by all imaging modalities, biphasic response was the best predictor of regional recovery of function (Odds ratio, OR: 9.9, 95% confidence intervals, 95% CI: 3.5–27.8). Conclusions: Although DSE and PET had overall comparable results, the presence of contractile reserve by the biphasic response to dobutamine was a best predictor for the improvement of LV contractile function in this group of patients.

Background: Doppler Tissue Imaging (DTI) has been evaluated in ischaemic heart disease and some cardiomyopathies. In patients with aortic stenosis (AS), left ventricular contraction is slowered. This study aimed to evaluate the possible role of the measurement of isovolumic contraction time (ICT) by DTI in the evaluation of AS severity. Methods: The study population constitutes 30 patients: 15 with AS (nine severe and six non-severe) and 15 control subjects. All of them had normal systolic function, sinus rhythm, and absence of ischaemic heart disease of conduction abnormalities. ICT was defined as the time from the onset of the QRS complex to the beginning of the DTI systolic wave. The correlation between ICT and aortic area obtained by continuity equation, as well as the diagnostic value of ICT in the identification of severe AS were studied. Results: ICT was significantly increased in patients with severe AS (98 � 27 versus 65 � 21 ms, p ¼ 0:024). There was a significant correlation between ICT and aortic area (r ¼� 0:56; p ¼ 0:035). The receiver operator characteristic curve of ICT in the identification of severe AS yielded an area under the curve of 0.852 (95% confidence interval: 0.665–1.0). The two best cut-points were [73 ms (88% sensitivity, 77% specificity) and [85 ms (78% sensitivity, 83% specificity). A value of[41 ms had a 100% sensitivity, but only a 17% specificity, and [91 ms showed a 100% specificity, but only a 44% sensitivity. Conclusions: ICT measured by pulsed-wave DTI is increased in patients with aortic stenosis. (Eur J Echocardiography 2003; 4: 279–285) 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.

Tumour angiogenesis and cellular pH regulation, mainly represented by Na(+)/H(+) antiporter exchange, have been heretofore considered unrelated subfields of cancer research. In this short review, the available experimental evidence relating these areas of modern cancer research is introduced. This perspective also helps to design a new approach that facilitates the opening and development of novel research lines oriented towards a rational incorporation of anticancer drugs into more selective and less toxic therapeutic protocols. The final aim of these efforts is to control cancer progression and dissemination through the control of tumour angiogenesis. Finally, different antiangiogenic drugs that can already be clinically used to this effect are briefly presented.

Objective: This study sought to evaluate the prognostic significance of the presence of DNA of Chlamydia pneumoniae in the coronary atherosclerotic lesions of patients with unstable angina. Background: C. pneumoniae has been implicated in the pathogenesis of coronary artery disease by serological and pathological studies, but whether antichlamydial antibodies and the presence of this pathogen in the coronary atherosclerotic tissue are related to prognosis in unstable angina remains unclear. Methods: A total 76 coronary specimens from 45 patients with unstable angina undergoing bypass surgery were subjected to nested polymerase chain reaction (PCR) for C. pneumoniae . Antichlamydial immunoglobulin G (IgG), A (IgA) and M (IgM) were also examined by an enzyme immunoassay. Patients were followed during a 2-year period to determine the incidence of adverse cardiovascular events. Results: DNA of C. pneumoniae was detected in 57 (75%) of 76 atherosclerotic lesions: 39 patients showed a positive PCR result in at least one plaque. Of the 45 patients, 44 (97.7%) showed a positive serological result: IgG was positive in 39 (86.6%) patients, IgM in five (11.1%) patients and IgA in 42 (93.3%). Clinical characteristics and serologic results were similarly distributed in patients with and without infected lesions at enrollment. At least one adverse event occurred in 21 (46.6%) of the 45 patients at 2 years: death in nine (20%), recurrent angina in 12 (26.6%), revascularization in six (13.3%) and myocardial infarction in two (4.4%) patients. The composite endpoint of death, myocardial infarction, recurrent angina and revascularization at 2-year follow-up did not differ according to the PCR or serologic results. Conclusions: The presence of C. pneumoniae in coronary atherosclerotic plaques of patients with unstable angina undergoing coronary bypass grafting does not have prognostic significance. In addition, serology does not allow us to differentiate those patients with plaque infection by C. pneumoniae and also does not provide any prognostic information in these patients.

Myocardial contrast echocardiography has recently been proposed as a valid technique in the evaluation of myocardial perfusion after myocardial infarction. The objective of this study was to evaluate the relation between changes in myocardial perfusion assessed by myocardial contrast echocardiography and left ventricular ejection fraction after myocardial infarction.We prospectively studied 17 patients with acute myocardial infarction, on whom two echocardiographic studies were performed, at 48-72 hours and at 6 months. Left ventricular ejection fraction and myocardial perfusion were evaluated with myocardial contrast echocardiography (Multiple-Frame Triggering and Harmonic Angio). Basal, medial and distal segments of the interventricular septum (anterior location infarction) and inferior wall (inferior infarction) were assessed. Myocardial perfusion was classified semi-quantitatively as grade 0, 1 or 2 (absent, heterogeneous or homogeneous opacification, respectively), giving a perfusion score.Left ventricular ejection fraction improved in 9 patients (53%), the proportion of grade 0 segments decreasing by 11 +/- 17%; by contrast, this proportion increased by 9 +/- 13% in patients with no improvement in ejection fraction (p = 0.028). Additionally, a significant correlation was observed between changes in ejection fraction and both perfusion score (r = 0.625; p = 0.007) and the proportion of grade 2 segments (r = 0.649; p = 0.005).After myocardial infarction, there is a significant relation between changes in left ventricular ejection fraction and myocardial perfusion assessed by myocardial contrast echocardiography with i.v. agents.

Background: Chlamydia pneumoniae has been associated with coronary artery disease by both seroepidemiological studies, and by direct detection of the micro-organism in atherosclerotic lesions. This bacteria could play a potential role in the development of acute coronary events. We examined coronary arteries from patients with unstable angina in order to verify an endovascular presence of C. pneumoniae, and to determine if there is any relationship between serology of acute infection by this pathogen and its presence inside the atherosclerotic plaque of these patients. Methods: We analysed a total of 76 atherosclerotic plaques obtained from 45 patients who underwent coronary artery bypass surgery. In all patients unstable angina was present within the prior 3 weeks. The presence of C. pneumoniae in the plaque was determined by nested polymerase chain reaction (PCR). Antichlamydial immunoglobulin G (IgG), A (IgA) and M (IgM) was examined by microimmunofluorescence and compared to the PCR result. Findings: DNA of C. pneumoniae was detected in 57 (75%) of 76 atherosclerotic lesions. In most cases (74/76: 97%) a positive IgA, IgM or IgG result was seen. Seven (12%) and 54 (94%) of the 57 PCR positive plaques came from patients with a positive IgM and IgA result, respectively. There was no statistical significant difference between PCR positive and PCR negative plaques in patients with a positive or negative serological result. Clinical characteristics were similarly distributed in patients with and without infected lesions. Interpretation: C. pneumoniae organisms are frequently found in the atherosclerotic lesions of patients undergoing coronary surgery for unstable angina. Neither serological results of acute or recent infection by C. pneumoniae nor clinical characteristics are useful in predicting the individual risk of harbouring C. pneumoniae in the coronary lesions of patients with unstable angina.

Interobserver variability is an important limitation of the stress echocardiography and depends on the echocardiographer training. Our aim was to evaluate if the use of contrast agents during dipyridamole stress echocardiography would improve the agreement between an experienced and a non-experienced observer in stress echo and therefore if contrast would affect the learning period of dypyridamole stress echo.Two independent observers without knowledge of any patient data interpreted all stress studies. One observer was an experienced one and the other had experience in echocardiography but not in stress echo. Two observers analysed 87 non-selected and consecutive studies. Out of the 87 studies, 46 were performed without contrast administration, whereas i.v. contrast (2.5 g Levovist by two bolus at rest and at peak stress) was administered in 41. In all cases, second harmonic imaging and stress digitalisation pack was used. The agreement between observers showed a kappa index of 0.58 and 0.83 without and with contrast administration, respectively.The use of contrast agents provides a better agreement in the evaluation of stress echo between an experienced and a non-experienced observer in stress echo. Adding routinely contrast agents could probably reduce the number of exams required for the necessary learning curve in stress echocardiography.

R econstruction of the ascending aorta by the composite graft technique is a widely accepted surgical approach in patients with aortic dissection or ascending aortic aneurysm. l Devastating complications including pseudoaneurysm formation and supravalvular aortic stenosis can occur, and may not be as infrequent as previously considered. Echocardiography is becoming the technique of choice in evaluating patients with aortic composite grafts and detecting its complications.* There

Left ventricular (LV) contraction is slowed in patients with aortic stenosis (AS). Although the possible role of LV systolic function abnormalities in the assessment of AS severity has been evaluated, current echocardiographic techniques cannot offer precise quantification of LV motion velocity. The study aim was to evaluate an automated segmental motion analysis (ASMA) system to assess AS severity.Twenty-two patients with AS, sinus rhythm and preserved LV ejection fraction were studied prospectively. Patients underwent both conventional Doppler echocardiography to measure transaortic gradient and aortic valve area by the continuity equation, and ASMA of the interventricular septum. The ASMA line graph mode displays changes in area through the cardiac cycle. The RR interval and time from the R-wave to peak maximum area shortening were measured, and an ASMA index was calculated.A significant and strong inverse correlation was found between aortic valve area and ASMA index (r = -0.78; 95% CI -0.90 to -0.55; p0.001). The area under the ROC curve in the diagnosis of severe AS (aortic valve areaor =0.8 cm2) was 0.97 (95% CI 0.90-1.0). Sensitivity, specificity, positive and negative predictive values and overall accuracy for an ASMA index0.40 were 100, 91.7, 92.3, 100 and 95.8%, respectively.The ASMA system may be valuable in evaluating AS, as it offers a strong correlation with aortic valve area calculated by the continuity equation, and very high sensitivity and specificity in the diagnosis of severe AS.

Infective endocarditis (IE) is a disease with a high morbidity and mortality during the active phase and a considerable risk of complications during follow-up. The aim of this study is to describe the clinical features of IE associated with perioperative mortality in patients undergoing surgery and the short- and long-term prognosis of this disease after surgical treatment.The clinical files of 150 patients (pts) admitted to our institution between 1989 and 2001 and whose final diagnosis was IE (Duke criteria) were retrospectively reviewed. Thus all patients included underwent at least 1 transthoracic examination, and a transesophageal examination if indicated. The study population was 69 patients with IE, 62 of whom (90%) underwent prosthetic valve replacement and 7 (10%) underwent explanation of pacemaker electrocatheter. In the statistical analysis, quantitative variables are expressed as means +/- SD and qualitative variables as proportions (percentages). Differences in survival were determined using the Kaplan-Meier log rank method. Associations were considered statistically significant when the p value was0.05.The mean age was 56 +/- 15 years. Thirty-five cases (51%) had prosthetic valve endocarditis, 30 (39%) had native valve IE and 7 (10%) pacemaker electrocatheter IE. Fifty-two patients (75%) had positive blood cultures. The most frequent agents were S. epidermidis (14.5%), S. aureus (14.5%), Enterococci (13%) and S. viridans (10%). Total perioperative mortality was 17.4% (n = 12), and surgical mortality was 19.4%. Our study shows a statistical tendency for higher mortality in diabetic patients (50% vs. 14%, p = 0.052) and in women (29% vs. 11%, p = 0.065). In multivariate analysis, the presence of heart failure was an independent predictor of perioperative mortality (OR = 11.4; 95% CI: 2.0-215.2; p = 0.024). Accumulated mortality in the first year was 28% and 5-year mortality was 48%.Prosthetic valve replacement in patients with IE is associated with high perioperative mortality (17.4%). Despite good early postoperative results, the mortality rate increases during the first year as well as the need for reoperation.

The incidence and severity of certain infections appear to be increased in patients with diabetes mellitus (DM). The study aim was to evaluate the effect of DM on short- and long-term outcome in patients with active infective endocarditis (IE).A total of 151 patients with IE was included and followed up for a mean of 3.1 years. Of these patients, 13 (9%) were diabetics. The outcome of patients with or without DM was compared at short-term (in-hospital) and long-term follow up.Patients with DM were older (66 +/- 11 versus 50 +/- 19 years, p0.01) and had a lower frequency of intravenous drug abuse (0 versus 30%, p0.01) and tricuspid valve involvement (0 versus 20%, p = 0.02) than non-DM patients. Mortality was higher in DM patients both in hospital (31% versus 15%, p = NS) and at a mean follow up of 3.1 years (54% versus 31%, p = 0.002). DM patients also had a significantly higher rate of cardiac failure (69% versus 38%, p = 0.03) and renal failure (62% versus 20%, p0.01) during hospitalization. Incidences of anatomic complications (abscess, pseudoaneurysm) (15.4% versus 20.3%), valve rupture or perforation (7.7% versus 16.7%) and need for surgical repair (46.2% versus 45.7%) were similar in both DM and non-DM patients. DM, without secondary pathology like renal failure, did not appear to be an independent risk factor for mortality at either short- or long-term follow up.Although mortality and morbidity in IE were greater in DM than in non-DM patients, diabetes itself does not constitute an independent risk factor.

Dobutamine echocardiography (DE), magnetic resonance imaging (MRI), and thallium redistribution (TS) are used to assess cardiac viability. However, these modalities sometimes yield contradictory results. Our aim was to establish the degrees of agreement among DE, MRI, and TS in identifying myocardial viability and to analyze the minimum critical mass of live (viable) cells required for each test to identify viability. A prospective study was done in which DE, MRI, and TS were consecutively performed in 10 ischemic patients scheduled for heart transplantation. The explanted heart was analyzed to quantify the amount of live cells per segment. The pathologic data were compared with the test results to analyze the minimum mass of viable cells required by each technique to identify viability. Mean age was 58 +/- 8 years (8 men). The mean ejection fraction was 0.27 +/- 0.04. Seven patients had severe cardiac failure (New York Heart Association functional class IV) and 6 patients had refractory angina. A total of 150 cardiac segments were analyzed. Among the 150 segments, 107 (71.3%) showed some degree of myocardial necrosis. Mean total area, mean fatty area, and mean necrotic area per segment were 2.53 +/- 0.7, 0.13 +/- 0.2, and 0.55+/-0.5 cm(2), respectively. As expected, a higher amount of necrotic tissue was found in nonviable segments. From the 150 segments, DE identified 90 as viable and 60 as nonviable. These data were similar to that of MRI (98 viable and 52 nonviable). A higher proportion of viable segments was found by TS (117 viable vs 33 nonviable). The concordance between DE and TS was only moderate (kappa 0.49). The agreement between MRI and TS also showed moderate concordance (kappa 0.56). The highest agreement was found between DE and MRI (kappa 0.73). Thus, discrepancies in assessing viability by DE, MRI, and TS may be due to differences in the minimum critical mass of live myocytes required by each technique to diagnose viability. Thallium requires a lesser amount of live tissue than DE or MRI to detect viability; also, its maximum diagnostic efficiency is obtained with lesser amounts of live tissue on each segment. These considerations should be taken into account when these diagnostic tests are used for the detection of viability before revascularization procedures.

Few trials have studied platelet activity during oral anticoagulation and all show a tendency for platelet aggregation to increase. This adverse effect has also been shown in some patients treated with unfractionated heparin, the so-called white clot syndrome. We studied platelet aggregation in patients with atrial fibrillation enrolled in the NASPEAF study and receiving antiaggregant, anticoagulant and both treatments.15 healthy control subjects (group C) and 99 patients were enrolled, the latter receiving 4 different antithrombotic regimens for platelet aggregation: group 1, 600 mg of the antiplatelet drug triflusal; group 2, anticoagulation for an INR of 2-3; and both treatments with 2 different levels of anticoagulation, mean INR of 1.85 (group 3) and of 2.15 (group 4). The same amounts of the agonists ADP, arachidonic acid and collagen were used in all tests. For statistical analysis we used the interval in min, from the addition of the agonist to the beginning of aggregation and the % of aggregation at 5 and 8 min.After arachidonic acid was given, the interval to the beginning of aggregation was shorter in group 2 than in group C: 0.6 +/- 0.21 and 1.1 +/- 1.2, and in both was significantly shorter than in the other three receiving antiplatelet drugs alone: group 1 = 1.58 +/- 1.4 or combined with anticoagulants: group 3 = 1.7 +/- 1.7 and group 4 = 2.4 +/- 2.1. The % of aggregation at 5 min, in groups C, 2, 1, 3 and 4 was respectively 48 +/- 24, 43.2 +/- 19, 29.6 +/- 17, 34.8 +/- 22 and 23.2 +/- 22.5. The data showed significantly increased platelet activity in groups C and 2 compared to groups 1, 3 and 4. Group 3 with a low anticoagulation level (mean INR = 1.85) showed a tendency to greater platelet activity than group 1 and 4 with p value = 0.08.The antiplatelet drug triflusal alone or combined with a therapeutic level of anticoagulation effectively reduces platelet aggregation and is not influenced by anticoagulant treatment. A low level of anticoagulation (INR2) shows a tendency to increase platelet activity.

Congenital quadricuspid aortic valve is very uncommon, and is often associated with other cardiac disorders, such as patent ductus, ventricular septal defect, pulmonary stenosis, mitral valve malformation, hypertrophic cardiomyopathy and coronary abnormalities. We report a patient with congenital quadricuspid aortic valve associated with congenital complete heart block. To our knowledge, this association has not been reported so far.

Background and Objective: The diagnosis of left ventricular pseudoaneurysm after acute myocardial infarction is usually based on echocardiography. However, this technique may have limitations in some patients, especially in cases with suboptimal acoustic window. The objective of this study was to evaluate the usefulness of contrast echocardiography in the diagnosis of left ventricular pseudoaneurysm after myocardial infarction. Methods and Results: The study population comprises six patients in whom a two-dimensional echocardiography showed an image consistent with left ventricular pseudoaneurysm. Levovist® (Schering) 4 gr was administered i.v. to more clearly visualize the blood flow from the left ventricle to the left ventricular pseudoaneurysm cavity in all patients. Infarct location was anterior in five patients, and posterolateral in one. No patient had received thrombolysis or primary angioplasty during the acute phase. The transthoracic echocardiographic study showed an echo-free space adjacent to left ventricle in all patients. In four cases, the diagnosis of left ventricular pseudoaneurysm was made before contrast administration. In the remaining two patients, the definite diagnosis was made only after Levovist® administration. Conclusion: In the diagnosis of postinfarction left ventricular pseudoaneurysm, the administration of contrast agents may be of help in the correct visualization of the blood flow from the left ventricle to the left ventricular pseudoaneurysm cavity, and may allow a definite diagnosis to be obtained in some patients. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved .

Objective: It has been reported that endocarditis in the elderly may have a poor outcome. Our aim was to assess the different features and prognosis, if any, in the present time. Methods: Of 103 patients with proven endocarditis, 31 were 65 years or older and 72 were younger than 65 years. Degenerative heart disease was seen more frequently in the elderly (22.5% vs 2.7%, P =.003). Drug abuse and immunodeficiency virus infection were more common in the younger group, as was tricuspid endocarditis (26.3% vs 0%, P P =.02) and leukocytosis (61.2% vs 40.2%, P =.049) were seen more frequently in the elderly. Results: Despite other similar clinical features, it took longer to diagnose older patients (7.2 ± 6.2 vs 3.2 ± 3.5 days, P Enterococcus infected the aged more often (32.2% vs 13.1%, P =.001). During hospitalization, heart failure and embolization tended to be more common in the elderly and the younger group, respectively. There were no significant differences in the incidence of anatomic complications, the need for operation, and overall mortality. Conclusion: Although a worse prognosis has been reported in elderly patients with infective endocarditis, the early use of transesophageal echocardiographic examinations and equal therapeutic options provides a similar outcome when compared with younger subjects. (J Am Soc Echocardiogr 2002;15:702-7.)

Dobutamine stress echocardiography is associated with a very low rate of serious complications, lower than 0.5% (death, infarction or sustained ventricular tachycardia). We report the case of a 75 year-old female patient that suffered a fatal left ventricular free wall rupture during a dobutamine stress echocardiography after acute myocardial infarction.

[corrected] Perioperative cardiovascular complications are an important cause of post-surgical morbility and mortality in patients undergoing major vascular surgery. Dobutamine Stress Echo is considered one of the methods of choice in the detection of coronary artery disease in this subgroup of patients.. Our aim was to analyze if dipyridamole stress echocardiography could be used as an alternative to Dobutamine Stress Echo in the perioperative evaluation of patients in need of major vascular surgery.The result of consecutives dypiridamole and dobutamine stress exams prior to vascular surgery were reviewed. We analyzed if those patients with a positive stress echo presented a higher number of cardiac events during and after surgery than those with negative stress echo. The negative and positive predictive values were calculated for both techniques.133 stress exams were analysed: 39 with dobutamine and 94 with dipyridamole. Of the 39 dobutamine studies 2 were positive, 29 negatives and 8 non conclusive. Of the 94 dypiridamole studies 13 were positive and 81 negatives. None of the patients with a positive dobutamine echo underwent surgery. The negative predictive value for dobutamine echo was 96.5%, quite similar to that of dypiridamole stress echo (97.5%).Dipyridamole stress echocardiography is a valid alternative to dobutamine echocardiography in the pre-surgical evaluation of patients undergoing major vascular surgery.

Treatment of Meniere's disease (MD) is still controversial and pressure changes transmitted to the inner ear have been reported to have effects similar to those of other non-surgical therapies. This paper reports on a clinical trial of MD patients which has been carried out using a portable piece of equipment, called Meniett, which delivers a pulsed, controlled, positive pressure to the middle ear, provided that a ventilation tube (VT) has previously been inserted. A comparison was made of the number of vertigo spells during the 2 months before treatment and during the 40-day treatment period. In addition, within this latter period a comparison was made between use of VT and use of VT + Meniett. Use of VT only had a positive effect in 90% of patients, with either absence (n = 10: 50%) or marked reduction (n = 8; 40%) in episodes of vertigo. When Meniett was also applied, stabilization of the positive effect on vertigo was registered, with a concomitant improvement in hearing threshold in 2 patients (10%). Although a longer and more reliable long-term follow-up of this treatment is needed, it is possible to propose the use of this therapeutic approach as it has been proven to induce a dramatic improvement in the symptoms affecting patients with Meniere's disease during reactivation of the disease.

Objective Dobutamine echocardiography and thalium 201 are useful in the assessment of myocardial viability, but both techniques frequently yield conflicting results. The objective of this study was to determine the minimum mass of viable myocardium that each test could detect and compare the agreement of dobutamine echocardiography and thallium 201 to detect viability. Methods Dobutamine echocardiography and thallium 201 were performed in 10 patients scheduled for cardiac transplantation. In each patient, 15 segments were studied. After transplantation these segments were analyzed by the pathologist measuring by a computer system the total area of each segment, the necrotic + fatty mass, and area (%) of viable myocytes per segment. The percentage of viable tissue was estimated ([Total mass – (Necrotic + Fatty tissue)]/Total mass × 100) on each segment, which was compared with the result (viable or not viable) obtained by echocardiography or thallium 201. Results Dobutamine echocardiography defined 90 segments (60%) as viable versus 117 (78%) in thallium (κ 0.49, 95% CI 0.36-0.63). The minimum percent of viable tissue per segment defined as viable by thallium was 43% versus 49% by echocardiography. With use of thallium, the highest accuracy of the test to detect viability was when the percent of necrotic tissue of the segment analyzed was 40% (positive and negative likelihood ratio 2.2 and 3.6, respectively). By use of echocardiography, the highest accuracy of the test was observed when the percent of necrotic tissue of the segment analyzed was 31% (positive and negative likelihood ratio 5.5 and 7.7, respectively). Conclusion The discrepant results of dobutamine echocardiography and thallium 201 are due to differences in the minimum mass of live myocytes required by each technique to detect viability. (Am Heart J 2002;143:157-62.)

Este artículo trata primero de definir y luego de llegar a un entendimiento profundo de la naturaleza íntima de los hiperdualismos detrás de las crisis actuales, desde el nivel personal, de la medicina y la ciencia hasta el modelo de la crisis política global. Se muestra cómo a todos estos niveles el estadio de pensamiento racionalista y el nivel de conciencia sistemático o del status quo, así como toda motivación egoica, no son suficientes para enfocar, comprender en profundidad y resolver desde la raíz la esencia y naturaleza multifactorial y multidimensional de los grandes problemas. Para lograrlo se defiende aquí la necesidad de acudir a un tipo de pensamiento supraparadójico y adual que permita concebir e integrar en grandes síntesis necesarias los diversos estadios de conciencia humana como paso ineludible para cambiar, en el sentido de mejorar, gran parte de la realidad externa. Para ello se propone un nuevo tipo de creatividad vocacional para cuya explicación nos apoyamos en grandes personalidades creadoras en las diversas áreas de la ciencia, la medicina, la literatura, el arte y el espíritu. Se consideran finalmente los estados alterados de conciencia y las profundas crisis psicológicas que pueden provocar las paradojas irresueltas así como los estancamientos y bloqueos emocionales en algunos de los seres más creativos, y cómo se han llegado a superar en ciertas ocasiones

severity of atherosclerotic involvement of the aortic valve and root in familial hypercholesterolaemia. Heart 1998;80:583–590. 7. Boon A, Cheriex E, Lodder J, Dessels F. Cardiac valve calcification: characteristics of patients with calcification of the mitral annulus and aortic valve. Heart 1997;78:472–474. 8. Shively BK, Roldan CA, Gill EA, Najarian T, Barton Loar S. Prevalence and determinants of valvulopathy in patients treated with dexfenfluramine. Circulation 1999;100:2161–2167. 9. Hensrud DD, Connolly HM, Grogan M, Miller FA, Bailey KR, Jensen MD. Echocardiographic improvement over time after cessation of use of fenfluramine and phentermine. Mayo Clin Proc 1999;74:1191–1197.

A 83 year old diabetic woman was admitted to our hospital with the diagnosis of subacute inferoposterior myocardial infarction. Four days later physical examination revealed a new systolic murmur at the left sternal border and apex. Transthoracic echocardiogram showed inferoposterior akinesis and a dissection tract in the posterior wall of the left ventricle arising from the distal to mid-segment with an entrance tear of 7 mm. Doppler color showed a systolic jet with a mosaic flow pattern inside the right atrium which appeared to originate in the coronary sinus. Transesophageal echocardiogram confirmed the intramyocardial dissection of the posterior wall and its communication with the coronary sinus, and identified the latter as the origin of the mosaic flow inside the right atrium. Medical treatment was initiated and the patient has been followed up for two years. The diameter of the entrance tear remains unchanged although the dissection tract and coronary sinus have enlarged, no significant enlargement has been observed in the right chamber on follow up.