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Background and Aims: About 20% of patients with germ cell tumor (GCT) are still resistant to therapy. To investigate which features are present in resistant patients, a multicenter study on GCT in children was undertaken to correlate clinical and laboratory parameters with the outcome., Methods: Patients aged less than 16 years, with histologically proven extracranial GCT were included., Results: Ninety-five patients (median age 33 months, 45 males) were eligible. The site of the primary tumor was gonadal in 59, extragonadal in 36. The stage was I in 39; II in 5; IIIa (microscopic residue) in 7; IIIb (macroscopic residue) in 16; IIIc (unresectable) in 13; IV in 15. The treatment was surgery alone in 31; surgery plus radiotherapy in 1; chemotherapy +/- surgery in 63. Post-chemotherapy resection in 19 (10 complete, 9 partial). The chemotherapy regimen was carboplatin 400 mg/m2/day on days 1, 2; etoposide 150 mg/m2/day on days 1, 2; ifosfamide 1,500 mg/m2/day on days 21, 22; dactinomycin 1.5 mg/m2/day on day 21; vincristine 1.5 mg/m2/day on day 21. Three patients died because of toxicity and two non-responders (to primary chemotherapy), died of progression; among the remaining 90 patients 20 relapsed, 9 are in second remission, 2 are alive with disease, and 9 died of disease progression (one from progression and intracranial hemorrhage). Overall survival was 82.7% and event-free survival: 71.5%. Survival according to: (a) site: testis: 100%; ovary: 88%; sacrococcyx: 69.6%; other sites: 33.3% (P < 0.001); (b) stage: I and II: 100%; IIIa: 83.3%; IIIb: 84.6%; IIIc: 60.6%; IV: 53.2% (P < 0.001); (c) AFP levels: normal: 85.5%; 42-9,470 ng/ml: 84.6%; >/=10,000 ng/ml: 58.7% (P = 0.02). All the pts who had complete resection of the primary tumor at diagnosis or at delayed surgery, remained in remission., Conclusions: Multivariate analysis showed that the primary site of tumor was the only independent prognostic factor for survival and EFS., (Copyright 2003 Wiley-Liss, Inc.)

Background: The aim of this study was to verify the changes in the autonomic balance by means of heart rate variability assessment in patients with myocardial infarction referred for cardiac rehabilitation., Methods: We studied 122 patients (79 males, 43 females, mean age 56 +/- 5 years), with a first uncomplicated myocardial infarction (anterior 48, thrombolysis 72), Killip class 1, preserved left ventricular function (ejection fraction 49 +/- 6%). All patients were free of inducible residual ischemia. Four weeks after myocardial infarction, patients were randomized into two groups; Group 1 (n = 58) referred for an 8 week cardiac rehabilitation program (scheduled: 24 sessions); Group 2 (n = 64): normal daily physical activity. During a 24-hour Holter ECG monitoring the following parameters were calculated in pharmacological wash-out at randomization (T0) and at the end of cardiac rehabilitation/control period (T1): mean value of RR intervals (RR), its standard deviation (SDNN), pNN50, rMSSD in the time domain; low frequency (LF) and high frequency (HF) value and the LF/HF ratio in the frequency domain. T1-T0 changes in percent values (delta %) were considered and compared between the two groups., Results: Thirty-one patients were excluded from the study either for insufficient adhesion to the cardiac rehabilitation program (< 13 sessions, 22 patients) or recurrent ischemia (3 Group 1 patients and 3 Group 2 patients) and non-assessable 24-hour Holter ECG monitoring (3 patients). Thirty-one Group 1 patients and 60 Group 2 patients completed the study with a first and a second 24-hour Holter ECG monitoring performed at 30 +/- 3 days and 60 +/- 4 days respectively. At the same time an ergospirometric test was performed to evaluate cardiopulmonary function by means of exercise time, maximum oxygen consumption, anaerobic threshold, exercise time at the anaerobic threshold, and maximum oxygen consumption at the anaerobic threshold. Twenty-eight Group 1 patients and 44 Group 2 patients completed the study with a first and a second ergospirometric test. Baseline heart rate variability parameters were comparable in the two groups. During the observation period only in Group 1 patients heart rate variability parameters changed significantly: RR (Group 1 = +18.3 +/- 21.3; Group 2 = +4.2 +/- 5.2, p = 0.000), pNN50 (Group 1 = 45.0 +/- 38.9; Group 2 = +24.2 +/- 34.7, p = 0.011), HF (Group 1 = +81.6 +/- 124; Group 2 = -28.7 +/- 75.4, p = 0.014) and LF/HF ratio (Group 1 = -26.0 +/- 16.1; Group 2 = -4.9 +/- 6.1, p = 0.062). There were no significant differences in SDNN, rMSSD and LF. A linear correlation between delta LF/HF ratio and baseline LF/HF ratio values was found in Group 1 (r = 0.489, p = 0.006), whereas no correlation was found between this parameter and age, ejection fraction, creatine phosphokinase, and infarct localization. Group 1 patients had a significant improvement in exercise tolerance compared to Group 2 patients., Conclusions: A cardiac rehabilitation program positively modifies the sympatho-vagal balance in patients with uncomplicated myocardial infarction, increasing the parasympathetic tone and exercise tolerance.

We analyzed the relation between dobutamine-induced Q-wave ST-segment elevation and regional contraction during low (5 to 10 microg/kg/min) and high doses (20 to 40 microg/kg/min) of dobutamine in a series of 391 dobutamine echocardiographic tests performed 10 +/- 2 days after a first uncomplicated acute myocardial infarction (AMI). ST-segment elevation was defined as > or = 1 mm new or additional J-point elevation with a horizontal or upsloping ST segment lasting 80 ms. Wall motion score index at rest was derived using a 16 segment-4 grade score model. Patients with dobutamine-induced ST-segment elevation had a higher wall motion score index at rest (anterior wall AMI: 1.67 +/- 0.27 vs 1.43 +/- 0.30, p = 0.0001; inferior wall AMI: 1.44 +/- 0.27 vs 1.30 +/- 0.18, p = 0.0001) and similar incidence and extent of myocardial viability and homozonal ischemia in comparison with those without ST-segment elevation. The sensitivity, specificity, and accuracy of dobutamine-induced ST-segment elevation for detecting residual homozonal ischemia were 51%, 55%, and 54%, respectively, in patients with anterior wall AMI, and 42%, 68%, and 58%, respectively, in patients with inferior wall AMI. In conclusion, dobutamine-induced ST-segment elevation is not associated with higher incidence and extent of viable or jeopardized myocardium but rather to a greater extent of wall motion abnormalities at rest. Thus, this finding does not represent a clinically reliable discriminator for selecting patients for coronary angiography and possible revascularization procedures.

Backgrounds: The aim of the study was to assess the relative prognostic accuracy of dobutamine echocardiography (TED) vs maximal bicycle exercise electrocardiography (TE) in patients with proven coronary artery disease., Methods: One hundred and thirty consecutive patients (70 patients with uncomplicated recent myocardial infarction, 19 asymptomatic patients with previous myocardial infarction and 41 patients with stable angina pectoris and previous myocardial infarction or previous myocardial revascularization procedure) underwent TED (incremental dobutamine infusion: 5 to 40 ncg/kg/min, continued with atropine 0.25 to 1 mg iv if necessary) and TE on different days and in random order. Criteria for positivity were: new or worsening regional dyssynergy for TED; ST segment shift > or = 1 mm from baseline for TE. End points were defined as spontaneous events (cardiac death, myocardial infarction and unstable angina) and total events (spontaneous events plus myocardial revascularization procedures)., Results: During 15.4 +/- 7.9 (range 1-33) months of follow-up, 33 events occurred: cardiac death (1), myocardial infarction (4) unstable angina (21) myocardial revascularization (7). Sensitivity, specificity, positive and negative predictive value, prognostic accuracy were similar for TED and TE (P = NS). Cumulative event-free survival curves as a function of TED and TE results were both statistically significant. A Cox stepwise regression analysis identified TED positivity obtained without atropine administration as the best predictor of spontaneous and total events (Odds ratio 5.33 and 4.38, respectively). Cumulative survival curves obtained by the combination of TED and TE results were statistically different (P < 0.05 and P < 0.001 for spontaneous and total events, respectively) and showed a poor clinical outcome in patients with both tests or only TED positive. TED correctly predicted clinical outcome in 24/39 patients in whom there was disagreement between the two tests., Conclusions: In patients with proven coronary artery disease, TED and TE have a similar accuracy for predicting clinical outcome. Where a discrepancy is seen between the two tests, TED appears to have a slightly higher prognostic value.

A multicentric retrospective study on leukemic ophthalmopathy (LO) is reported. It includes 21 patients, 16 males and 5 females, with acute leukemia (AL) observed in 10 SIOP centers. LO developed in three patients at the time of diagnosis of AL; five patients were in first complete remission (three off therapy); four patients were in second or third remission; and nine were in combined relapse. Most frequent symptoms were blurred vision, photophobia, and ocular pain. Two patients with acute nonlymphoblastic leukemia died before treatment; another underwent bone marrow transplantation; one patient with B-cell acute lymphoblastic leukemia (B-ALL) treated with chemotherapy and radiotherapy died 4 months after LO; the remaining 17 children were treated according to different schedules with (10) or without (7) radiotherapy on the affected eye. Twelve patients achieved ocular remission and four of these had a second ocular relapse. Complete remission after LO treatment lasting for more than 3, 7, 24, 29 months was observed in four patients. The authors conclude that cure is possible in patients who had LO in first complete remission treated with chemotherapy and radiotherapy at high dose on the affected eye.

Fifteen patients at a mean age of 58 underwent adenosine and maximal exercise thallium SPECT imaging. All scans were performed 1 week apart and within 4 weeks of cardiac catheterization. SPECT imaging was performed after the infusion of 140 micrograms/kg/min of adenosine for 6 minutes. Mean heart rate increment during adenosine administration was 67 +/- 3.7 to 77 +/- 4.1. Mean blood pressure was 136 +/- 7.2 to 135 +/- 6.2 systolic and 78 +/- 1.8 to 68 +/- 2.6 diastolic. No adverse hemodynamic effects were observed. There were no changes in PR or QRS in intervals. Five stress ECGs were ischemic. No ST changes were observed with adenosine. Although 68% of the patients had symptoms of flushing, light-headedness, and dizziness during adenosine infusion, symptoms resolved within 1 minute of dosage adjustment or termination of the infusion in all but one patient, who required theophylline. Sensitivity for coronary artery detection was 77% and specificity 100%. Concordance between adenoscans and exercise thallium scintigraphy was high (13/15 = 87%). In two patients, there were minor scintigraphic differences. The authors conclude that adenosine is a sensitive, specific, and safe alternative to exercise testing in patients referred for thallium imaging and may be preferable to dipyridamole.

In a retrospective study correlating the degree of tricuspid regurgitation seen on first-pass radionuclide angiography with that seen on contrast right ventriculography in 51 patients, ten had no tricuspid regurgitation by contrast ventriculography, whereas by radionuclide angiography nine had no regurgitation and one had minimal regurgitation. Of eight patients with minimal tricuspid regurgitation by contrast ventriculography, five had minimal regurgitation by nuclide angiography and three had no regurgitation. Of the 11 patients with mild to moderate tricuspid regurgitation by contrast studies, ten had mild to moderate regurgitation and one had severe regurgitation by nuclide angiography. Of 22 patients with moderate to severe tricuspid regurgitation by contrast studies, 15 had moderate to severe regurgitation and seven had mild to moderate regurgitation by nuclear angiography. In this preliminary study comparing radionuclide angiography with contrast right ventriculography, there were three false-negative and one false-positive nuclide angiograms, giving a sensitivity of 93% and a specificity of 90%.

First pass radionuclide angiography (RA) was used to assess its ability to detect and quantitate the presence of left-sided regurgitation due to isolated mitral regurgitation (MR). In this study the nuclear regurgitant fraction (NRF) obtained from first pass RA was correlated with the results of contrast ventriculography (CV) in 50 patients, 18 with and 32 without MR. The correlation between CV and RA in the confirmation and quantification of isolated MR revealed a sensitivity of 100 percent and a specificity of 97 percent in patients with LVEF greater than or equal to 35 percent.

The effects of elective saphenous vein coronary artery bypass surgery on left ventricular ejection fraction were assessed by using exercise first-pass radionuclide angiography in 66 consecutive patients. All patients with left main coronary artery or concomitant valvular disease were eliminated from the study. Before surgery, 7 patients had normal postexercise left ventricular function (Group 1), 33 had normal resting left ventricular function with an abnormal response to exercise (Group 2), and 26 had an abnormal resting left ventricular ejection fraction with an abnormal response to exercise (Group 3). Following surgery, patients in all three groups had no change in mean resting left ventricular ejection fraction; however, patients in Groups 2 and 3 had significant improvement in mean postexercise left ventricular ejection fraction (p less than 0.0001 and p less than 0.0054 respectively), whereas patients in Group 1 did not. Previous studies reported improvement in postexercise ejection fraction in patients with reduced resting left ventricular function and with an ischemic response to exercise (Group 3). But this is the first study to confirm improvement in postexercise function in patients with normal resting function and an ischemic response to exercise (Group 2).

Eight patients, mean age 72 years, with aortic valve stenosis were studied by ultrafast CT 1 day after cardiac catheterization. After injection of radiographic contrast material through a peripheral vein, two contiguous eight-level R wave-triggered cine mode scans in the short axis were acquired, starting above the aortic valve and continuing through the apex of the left ventricle. Seven of eight patients, all with calcified aortic valves, had a detectable central orifice. Catheterization-derived aortic valve areas were within 0.25 cm2 of the CT valve areas in six of seven. LV mass was measured by ultrafast CT in the eight patients with aortic valve stenosis (121.6 +/- 18.2 gm/m2) and was found to be significantly higher (p less than 0.0001) than that in a group of eight subjects with normal LV function, no history of hypertension, and normal ECGs (73.0 +/- 13.1 gm/m2). It is concluded that in selected cases ultrafast CT can contribute to the assessment of severity of calcific aortic stenosis by measurement of LV mass and valve area.

The changes in right ventricular (RV) and left ventricular (LV) function and in regurgitant fractions on first-pass exercise radionuclide angiography (RNA) were assessed in 29 consecutive patients with symptomatic mitral valve prolapse (MVP). The mean right ventricular ejection fraction (RVEF) was 35 +/- 8% at rest and 46 +/- 15% after exercise (p less than 0.001). The mean left ventricular ejection fraction (LVEF) was 62 +/- 11% at rest and 74 +/- 13% after exercise (p less than 0.001). Seven of 29 patients had an abnormal RV response and 6 had an abnormal LV response. Eight had abnormal wall motion after exercise. A total of 12/29 patients (41%) had one or more abnormalities. The mean left-sided regurgitant fraction before exercise was 27 +/- 17% in 21/29 patients (72%) and 31 +/- 21% after exercise (p = ns). An additional 5 patients (17%) developed left-sided regurgitation after exercise. These findings indicate that wall motion abnormalities and abnormal RVEF and LVEF responses to exercise occur in symptomatic MVP patients. In addition, 26/29 (89.6%) had left-sided regurgitation after exercise. Since the presence of a murmur did not correlate with the presence of mitral regurgitation by RNA, then symptomatic patients with MVP should have first-pass exercise RNA to assess the presence of regurgitation at rest and after exercise. Antibiotic prophylaxis is recommended in MVP patients with systolic murmurs or with regurgitation. Since patients without murmurs can have regurgitation, further study is necessary to determine the need for endocarditis prophylaxis in these patients.

During a three-year period, complete revascularization of diffusely diseased left anterior descending (LAD) coronary arteries was accomplished by extensive endarterectomy in conjunction with bypass grafting in 37 patients in whom conventional bypass was not feasible. This group constituted 7.0% of all patients undergoing nonemergency coronary revascularization during this period. The left internal mammary artery was used to bypass the endarterectomized LAD artery in 22 patients. There was 1 (2.7%) operative death and 1 perioperative myocardial infarction. At follow-up, which was 100% with a mean of 41.4 months, all endarterectomy patients were in New York Heart Association Functional Class I or II. Twenty-four endarterectomy patients underwent first-pass radionuclide angiographic stress testing 20 months after operation. Twenty patients (83%) had excellent postoperative exercise tolerance, achieving 5 to 7 mets on treadmill testing. Left ventricular functional reserve was preserved, as evidenced by an increase of global ejection fraction from 48 +/- 15% at rest to 59 +/- 18% (p less than 0.005) with exercise. A similar increase was measured in the proximal and distal anterior wall segmental ejection fractions. No difference in response to exercise was found between the internal mammary artery and the vein graft groups. Thus, complete revascularization of the diffusely diseased LAD artery can be accomplished by adjunct endarterectomy without added morbidity or mortality and with excellent functional results.