Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study).

BACKGROUND: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse. METHODS: In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials. RESULTS: Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival. CONCLUSION: In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial.

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group.

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.

[Acute lymphoblastic leukemia in childhood. A 10-year experience with the DFCI 81-01 protocol]. / Leucemia linfoblástica aguda na criança. Experiência de dez anos com o protocolo DFCI 81-01.

Acute lymphoblastic leukemia is the most frequently encountered pediatric cancer. Approximately 70% of cases can be cured of the disease. In this article, we describe the experience of our Center in the last ten years with a treatment protocol adapted from protocol DFCI 81-01 (from the Dana Farber Cancer Institute, Boston). We conclude that it is easily accomplished, well tolerated and that it allowed us to significantly improve the outcome of our patients (80% 5 year-survival). Nevertheless, we are currently in the process of changing to a new protocol--one that will hopefully achieve a comparable cure rate with less long-term toxicity.

[Incessant atrial tachycardia and peripartum cardiomyopathy--a therapeutic challenge]. / Taquicardia auricular incessante e miocardiopatia peripartum--um desafio terapêutico.

Peripartum cardiomyopathy is an uncommon cause of heart failure but with serious prognosis. We report the case of a patient with peripartum cardiomyopathy presenting acute heart failure (severe biventricular systolic failure) and incessant atrial tachycardia, a rare arrhythmia difficult to control, that was responsible for cardiogenic shock, fetus death and multiple organ failure: renal failure (hemodialysis during 17 days), respiratory and hepatic failure and ischemic acute cholecystitis (treated surgically). After emergency cesarean section, heart rate control was obtained only after administering verapamil. Progressive clinical improvement with total recovery of hepatic and renal functions followed under treatment with vigorous multiple organ support. Six months after referral, the patients is doing well with normal daily life controlled with conventional therapy for heart failure, in stable sinus rhythm. Echocardiography shows a dilated left ventricle with partial resolution of systolic dysfunction rhythm. Echocardiography shows a dilated left ventricle with partial resolution of systolic dysfunction. The use of verapamil in severe biventricular systolic failure is discussed.

[Electrocardiographic changes after coronary angiography: effect of the contrast media used]. / Alterações electrocardiográficas após coronariografia: influência do contraste utilizado.

UNLABELLED: Prospective study to evaluate the influence of 2 different iodine contrasts (used in coronariography) on the electrocardiographic changes recorded after intra-coronary injection. MATERIAL AND METHODS: Sixty-six patients (pts) - 50 men and 16 women - 59 +/- 4 years underwent coronariography to confirm and/or evaluate coronary artery disease (CAD). Group I (33 pts) received a hyperosmolar contrast; group II received a low osmolarity contrast. The electrocardiograms were recorded during and until 20 seconds after intra-coronary injection, in standard leads and V5. Tracings were analysed regarding the development of: arhythmias, mean axis deviation and QRS enlargement - type A abnormalities; ventricular repolarization (ST/T) changes - type B abnormalities. ECG changes were compared with: 1. contrast used; 2. presence (or absence) of CAD; 3. correlation between type B abnormalities and the arteries affected. RESULTS: 1. a) Twenty nine pts (88%) of group I had A and/or B electrocardiographic changes, compared with 16 (48%) of group II (p < 0.01). b) There were type A changes in 13 pts of group I (39%) versus 3 pts (9%) of group II (p < 0.01). c) Type B changes were present in 25 pts (76%) of group I and in 20 pts (60%) of group II (p-NS). 2. a) Type A abnormalities were recorded in 13 of 48 pts with CAD (27%) against 3 of 18 (17%) cases with normal coronariography (p-NS). b) Type B abnormalities were present in 30 of 48 pts (63%) with CAD and in 10 of 18 cases (56%) of people with normal coronariography (p-NS). 3. In 21 pts with isolated right (or left) CAD, contrast injection in the right coronary artery induced type B ECG changes on the homo-lateral supplied territory in 14 cases, no change at all in 4 cases and changes in the contra-lateral area in only 3 pts. Injections in the left coronary artery produced similar results. CONCLUSIONS: 1. Hyperosmolar contrast produced significantly more electrocardiographic abnormalities, mainly type A, than low osmolarity contrast. This one may be, therefore, preferable. 2. Both types of electrocardiographic changes were equally recorded in pts with CAD and in people with normal coronariography. 3. Type B changes seem to be related with the location of the injection, irrespective of the presence or absence of coronary artery disease.

Postexercise changes of the QTc interval in patients with recent myocardial infarction.

A lack of the QTc ratio decrease at maximal exercise is considered as an index of exercise-induced ischemia in patients with coronary artery disease. The authors studied 51 patients with recent myocardial infarction in order to evaluate the QTc changes with exercise in assessing the presence of remaining ischemic myocardium. All patients were submitted to exercise stress tests, coronary angiographies, and exercise thallium 201 scintigraphies within 3-5 months of the myocardial infarction. Of the patients studied, 18 showed one-vessel disease and 33 showed multivessel disease. All vessels were classified as patent or occluded. In all patients with reversible thallium 201 defects both at distance and in the infarct zone, the QTc interval following exercise either showed a prolongation or no change from the resting electrocardiogram. In patients with only fixed perfusion defects, the QTc shortened at the end of the test. This study showed a low sensitivity and specificity for inducible ST-segment depression compared with the delayed redistribution on the postexercise thallium 201 scintigram. QTc variations at the end of exercise electrocardiograms are valuable as a noninvasive, low-cost identification of residual ischemic myocardium in patients after myocardial infarction.

[Significance exercise-induced ST elevation in patients with myocardial infarction]. / Significado do supradesnivelamento ST de esforço em doentes com enfarte do miocárdio.

In 52 patients with previous myocardial infraction, 49 men and 3 women (mean age 56 +/- 7.1 years) the significance of ST-segment elevation during the stress-test, was evaluated. Of the 52 patients 15 (29%) showed St-segment elevation and 37(71%), showed no alteration of the ST-segment. Extension of coronary disease, degree of obstruction, wall motion abnormalities and the presence of residual ischemia were evaluated by coronary angiography, technetium-99M pyrophosphate imaging and exercise TL-201 scintigraphy. From the results of the study one may conclude that, in patients with previous myocardial infraction exercise, ST-segment elevation is a consequence of sub-occlusion of the left anterior descending coronary artery with severe ventricular dysfunction either in patients with one or multiple vessel disease.

[Value of the ergometric test after myocardial infarction]. / Valor da prova ergométrica no pós-enfarte do miocárdio.

Exercise stress testing (EST) after myocardial infarction helps to define the clinical subsets of patients at high and low risk. It should be performed before hospital discharge, unless a contraindication exists. In order to exclude false positives, EST must be repeated 4-6 weeks later. EST helps to recognize the presence of residual ischaemia. Significant ST segment depression during exercise, associated or not with angina, is the most important indicator of ischemia. These patients with ischaemia at distance i.e., those with ST segment changes in ECG leads without W waves, are at high risk. Some continuous exercise variables (degree of ST deviation, time of recovery and exercise duration) are related to cardiac mortality. Exercise induced complex ventricular arrhythmias seem to be related to left main or three vessels disease, and a greater likelihood of sudden death, particularly when coexist a low ejection fraction, important segmentar disturbances of contractility and ST segment depression. EST after myocardial infarction has great value to assess the results of medical therapy and/or coronary angioplasty or bypass grafting. EST also constitutes a valuable clinical tool to support a comprehensive rehabilitation programme.

[Maximal values of serum creatine phosphokinase and its myocardial fraction in acute myocardial infarct. Correlation with a previous history of ischemic cardiopathy]. / Valores máximos de creatinafosfoquinase sérica e sua fracção miocárdica no enfarte agudo do miocárdio. Correlação com história prévia de cardiopatia isquémica.

OBJECTIVE: To evaluate the importance of preinfarction angina as a determinant of infarct size. DESIGN: Retrospective study of patients (pts) with acute myocardial infarction (AMI). SETTING: Patients admitted to an Intensive Care Unit of a University Hospital. PATIENTS: The study concerns 224 pts, 161 men women, aged 63.09 +/- 11.92 years, who did not receive thrombolytic or intravenous beta-blocking therapy and in whom it was possible to establish the presence or absence, of previous ischemic heart disease. METHODS: Patients, were divided in 2 groups: A (1st AMI, 172 dts - 123 M, 49 F) and B (2nd AMI, 52 dts - 38 M, 14 F). These groups were subdivided according the presence of preinfarction angina (A1, B1) or its absence (A2, B2). The infarct size was evaluated by peak values of CK/CKMB. RESULTS: Group A: CK/CKMB--959/101; Group B: CK/CKMB--742/77 (p-NS). Subgroups--A1: CK/CKMB--1143/118; A2: CK/CKMB--725/78 (p less than 0.001); B1: CK/CKMB--635/59; B2: CK/CKMB--818/88 (p-NS). The analysis of CK/CKMB values distribution, according to the affected cardiac wall, has shown an identical correlation. CONCLUSION: 1--The larger infarct size in subgroup A1 (1st AMI without angina) suggests a protective effect by collateral circulation in subgroup A2 (1st AMI with angina). 2--The larger infarction (although not significantly) in group A (1st AMI), correlates with less viable muscle in group B (2nd AMI). 3--The higher values of CK/CKMB in group B2 (2nd AMI with angina) can be expected given the presence of residual ischemia. 4--The absence of the protective role by collateral circulation in patients of subgroup A1 (1st AMI without angina) suggests for them a stronger indication for thrombolytic therapy.

[Congestive heart insufficiency as the end-stage of several nosologic entities]. / A insuficiência cardíaca congestiva como estádio terminal de várias entidades nosológicas.

Heart failure is the final state of virtually all forms of primary or secondary heart disease. In this abnormal pathophysiological syndrome, a wide spectrum of clinical physiological cardiac states (congenital, valvular, rheumatic, hypertensive, coronary and cardiomyopathic) as well as some hyperkinetic circulatory/metabolic states leads to a low, normal or even high cardiac output--inadequate, however, in front of the requirements of the metabolizing tissues. In this revision article the A.A. successively consider the main causes of cardiac-circulatory failure, pointing out, at the end, the usefulness of recognizing the underlying and the precipitating causes of heart failure, in order to rapidly establish the appropriate therapeutic and preventive approaches. Four clinical cases are presented illustrating some of the underlying "treatable" causes of heart failure systemic hypertension, iatrogenic hypophosphatemia, chronic alcoholism and hemochromatosis.

[The heart in Papio erxleben, 1777. II. Study of the atrioventricular node region in P. cynocephalus L., 1766]. / Le coeur de Papio Erxleben, 1777. II. Etude de la région jonctionnelle atrioventriculaire chez P. cynocephalus L., 1766.

The present work studies the atrioventricular (AV) junctional area in 15 hearts of P. cynocephalus perfused with phosphate-buffered formal 10%; 12 hearts were studied by gross anatomy and mesoscopic dissection, 3 hearts were serial sectioned in frontal plane (10 micron) and stained by trichromic method. The results show that the junctional AV area in P. cynocephalus is approximately similar to the same region in M. fascicularis and also in the human heart (Mandarim-de-Lacerda et Penteado in press, Mandarim-de-Lacerda et Hureau in press). It was impossible to dissect the AV node and AV bundle while the left bundle branch was easily identified as a calibrous fan-like fashion on the left side of the interventricular septum. The right bundle branch left the AV bundle and penetrated the myocardium of the trabecula septo-marginalis (moderator band).