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G Specchia

Publications and source records attributed to G Specchia.

At least 73 records · Page 4Linked to original sources

Identification of new partner chromosomes involved in fusions with the ETV6 (TEL) gene in hematologic malignancies.

Several partner genes on different chromosomes have been reported to be fused with the ETV6 gene (located in chromosome band 12p13), with different breakpoints and different frequencies, in various hematologic malignancies, particularly acute myeloid and lymphoid leukemias and myelodysplastic syndromes. By using FISH and molecular analyses, we have analyzed five different pediatric and adult patients carrying cytogenetic abnormalities involving 12p13. Our findings demonstrate that ETV6 was rearranged in all the cases analyzed. In particular, ETV6 was disrupted by translocations with chromosomal bands 7q22, 7q36, 9q11, and 13q12, not previously described as partners of ETV6 in translocations, thus extending its promiscuity in rearranging with different partner genes.

Adult↗

T-cell acute lymphoblastic leukemia occurring in a patient with acute promyelocytic leukemia.

Secondary acute lymphoblastic leukemia (sALL) following acute myeloid leukemia (AML) is a rare event; only eight cases have been reported. We report a patient with acute promyelocytic leukemia (APL), in hematological and molecular remission who developed T-ALL three years after the diagnosis of APL. The morphological, cytochemical, phenotypical and molecular features of this T-ALL were different from those of the previous APL. The absence of t(15;17), negative PML/RAR alpha at reverse transcription polymerase chain reaction (RT-PCR) analysis and presence of TcR delta support the hypothesis that the T-ALL in this sALL case originated from a different clone from that of the APL cells.

Adult↗

Mental status and pain perception during stressor tests in patients with coronary artery disease.

Asymptomatic myocardial ischaemia is frequently observed in patients with coronary artery disease (CAD), both during daily life and during stressor tests. Psychological mechanisms seem to be involved in the lack of pain during myocardial ischaemia. The aim of this study was to verify in a selected population of CAD patients whether mental status might influence the pain perception during different stressor tests. The study population contained 73 male patients (mean age 52+/-8 years) with stable angina during daily life, reproducible exercise-induced myocardial ischaemia during ergometric stress test (EST) and angiographically documented CAD. All patients underwent cold pressor test (CPT), mental arithmetic stress test (MST), hyperventilation test (HT) and mental stress in association with cold pressor test (combined test, MST + CPT). During the stressor tests, myocardial ischaemia was induced in 15/73 (21%) patients by CPT, in 18/73 (25%) by MST, in 15/73 (21%) by HT and in 19/73 (26%) by MST + CPT. Out of the patients with stressor test-induced myocardial ischaemia, silent ischaemia was observed in 43/73 (59%) during EST, in 10/15 (67%) during CPT, in 16/18 (89%) during MST, in 7/15 (47%) during HT and in all patients during MST+CPT (100%). Among the ischaemic symptomatic patients during stressor tests, the lowest anginal pain intensity was experienced during MST (4.0+/-2.2) and the highest during EST, both at peak exercise and at the ischaemia threshold (6.6+/-2.9 and 5.9+/-2.7, respectively, p<0.05). During MST, the prevalence of silent ischaemia was higher than was observed during the other tests. All study patients remained asymptomatic when myocardial ischaemia was induced by MST + CPT. Even the intensity of CPT induced hand pain was significantly higher during CPT alone than during MST+CPT. These results confirm that mental status may influence pain modulation.

Journal Article↗

Factors increasing the risk of allograft vascular disease in heart transplant recipients.

Allograft vascular disease is the major cause of late cardiac graft failure. A multifactorial etiopathogenesis is supposed. Our study investigated factors associated with allograft vascular disease occurrence. After stratifying our series on the basis of potential risk factors, we calculated allograft vascular disease incidence rate in 267 grafts from 258 patients who underwent transplant between November 1985 and August 1996. Chi-square test was used for the identification of univariate risk factors to be included in a multivariate model. Multivariate analysis was based on a Poisson model. Seventy of the 267 grafts (26.2%) were diagnosed with allograft vascular disease. Heart disease other than idiopathic dilated cardiomyopathy, donor's age, number of mismatches for HLA-B = 2, presence of systo-diastolic hypertension, number of acute rejection positive endomyocardial biopsies > or = 7 and the association of human Cytomegalovirus and hepatitis C virus infections proved to be univariate risk factors, and were included in the Poisson multivariate model. The association of Cytomegalovirus and hepatitis C infections multiplied allograft vascular disease incidence rate by 3.9, systo-diastolic hypertension by 2.2, occurrence of 2 HLA-B mismatches by 2, a high number (> or = 7) of acute rejection positive-endomyocardial biopsies by 1.8, and heart disease other than idiopathic dilated cardiomyopathy by 1.8. The association of human Cytomegalovirus and hepatitis C virus infections, of HLA-B mismatches, of acute rejection-positive endomyocardial biopsies, as well as post-transplantation hypertension and native heart disease other than idiopathic dilated cardiomyopathy, proved to be positively associated with an increased risk of allograft vascular disease. Given the concordance of our data with those of numerous prior series, we are going to adopt a special surveillance angiographic protocol for patients with these factors.

Adolescent↗

Frequency and characteristics of coronary thrombosis in the epicardial coronary arteries after cardiac transplantation.

We investigated at autopsy or at retransplantation the frequency and characteristics of coronary thrombosis in 76 cardiac allografts: 37 in place for < or = 2 months (early) and 39 in place >2 to 99 months (late). The 76 allografts were inserted in 69 patients: a single 1 in 56 patients and 2 allografts in 13 patients, 7 of whom subsequently died and had an autopsy. An average of 140 sections from 70 5-mm-long segments of 8 epicardial coronary arteries were examined from each of the 76 allografts with both hematoxylin-eosin and Movat pentachrome stains. Thrombus was found in only 1 coronary artery (3%) (the right one) of the 37 early allografts, and in 24 of 39 late allografts (61%). Of the latter 39 grafts, 29 (79%) had allograft vascular disease (AVD) and 24 (83%) of them had coronary thrombosis. Of the 312 epicardial coronary arteries (4 major and 4 minor) examined in the 39 late cases, 66 arteries (21%) contained thrombus. Of the 24 late cases with thrombus in at least 1 artery, thrombus was present in 66 (34%) of the 192 epicardial coronary arteries examined: in 6 of the 8 arteries in 3 patients; in 5 arteries in 2 patients; in 4 arteries in 1 patient; in 3 arteries in 5 patients; in 2 arteries in 6 patients, and in a single artery in 7 patients. In all 66 arteries with thrombus (24 patients) the thrombus was longer than 5 mm. The thrombus in the late cases was entirely nonocclusive (mural) in 51 (77%) of the 66 epicardial coronary arteries containing thrombus and entirely occlusive in 10 arteries (15%). It consisted exclusively of multiluminal channels in 6 arteries (9%) and combinations in 1 artery (2%). Acute myocardial infarcts were present in 3 patients, all of whom had occlusive thrombi. In all 10 arteries with occlusive thrombi, the thrombus was larger than the underlying plaque and no occlusive thrombi were located over ulcerated plaques. These observations demonstrate that thrombus is common in epicardial coronary arteries >2 months after cardiac transplantation.

Adolescent↗

Expression of neutrophil and monocyte CD11B/CD18 adhesion molecules at different sites of the coronary tree in unstable angina pectoris.

To assess the site of leukocyte activation in unstable angina, the expression of neutrophil and monocyte CD11B/CD18 adhesion molecules in 26 patients was measured from blood samples taken from the coronary ostium, the coronary sinus, and the coronary artery just distal to the culprit lesion (postobstructive chamber). CD11B/CD18 adhesion molecules detected by direct immunofluorescence evaluated by flow cytometry were significantly higher in the coronary sinus blood than in both the coronary ostium and the postobstructive chamber blood, suggesting that leukocyte activation takes place at the microcirculatory interface with the injured myocardium, probably as the result of short but repeated episodes of myocardial ischemia.

Adult↗

Interaction between exercise training and ejection fraction in predicting prognosis after a first myocardial infarction.

BACKGROUND: Although recent meta-analysis trials have shown that exercise training may improve survival after myocardial infarction, the mechanism of this beneficial effect is still unknown. The purpose of this study was to detect possible interactions between exercise training and predictors of prognosis after a first myocardial infarction. METHODS AND RESULTS: Patients with uneventful clinical courses after a first myocardial infarction were randomly assigned to a 4-week training period (125 patients, group 1) or to a control group (131 patients, group 2). Before randomization, all patients underwent a symptom-limited exercise test (28 +/- 2 days after myocardial infarction), 24-hour Holter monitoring, and coronary arteriography (31 +/- 3 days after the acute episode). After a mean follow-up period of 34.5 months, 18 patients had cardiac deaths (5 in group 1 and 13 in group 2). Multivariate analysis by Cox regression model showed that ejection fraction was the only independent prognostic indicator (P = .03). Evidence existed of an interaction between ejection fraction and exercise training, showing an effect of physical training on survival that depended on the patient's ejection fraction. Among patients with ejection fractions < 41%, the relative risk for an untrained patient was 8.63 times higher than for a trained patient (P = .04), whereas for ejection fractions > 40%, the estimated risks for trained and untrained patients were similar. CONCLUSIONS: These data show that exercise training may prolong survival in post-myocardial infarction patients with depressed left ventricular function. A randomized trial in such patients seems warranted.

Adult↗

Patency of infarct-related artery. Effect of restoration of anterograde flow on vagal reflexes. ATRAMI (Automatic Tone and Reflexes After Myocardial Infarction) Investigators.

BACKGROUND: In post-myocardial infarction (MI) patients, the restoration of anterograde flow in the infarct-related artery (IRA) significantly improves survival. Limitation of infarct size and increased electrical stability of the myocardium are likely operating mechanisms for this beneficial effect. We tested the hypothesis that patency of the IRA may enhance vagal reflexes, a factor known to affect electrical stability of the infarcted myocardium. METHODS AND RESULTS: Analysis of angiographic data was performed in 359 of 1284 post-MI patients enrolled in a multicenter prospective study within 8 weeks after the index MI. All the patients underwent baroreflex sensitivity (BRS) assessment by the phenylephrine method. The BRS of the entire population averaged 8.2+/-5.5 ms/mm Hg and was significantly related to age but not to ejection fraction (EF). One-, two-, and three-vessel disease was present in 138, 96, and 99 patients, respectively, while no coronary stenosis was observed in 26. IRA patency was documented in 234 patients (65%), while in the remaining 125 (35%), the artery remained occluded. Patients with occluded IRAs had more extensive coronary disease (2 to 3 vessels, 71% versus 46%, P<.01) and more depressed left ventricular (LV) function (LVEF, 48+/-13% versus 53+/-12%, P<.001). Patency of the IRA was associated with higher BRS values (BRS, 8.9+/-5.8 versus 7.1+/-4.7 ms/mm Hg, P<.005) and with a lower incidence (9% versus 18% P<.02) of markedly depressed BRS (<3 ms/mm Hg), a condition suggested by preliminary studies to be associated with an increased risk of post-MI mortality. The association between IRA patency and BRS was more evident in anterior than in inferior MI. Multivariate regression analysis showed that age of the patient and patency of the IRA were the major independent determinants of BRS, while LVEF was weakly related to BRS and only when analyzed as a categorized variable. CONCLUSIONS: The presence of an open IRA is associated with higher baroreflex sensitivity, and this effect is largely independent of limitation of infarct size by IRA patency. These data offer new insights into the mechanisms by which coronary artery patency may affect cardiac electrical stability and survival.

Adult↗

Correlation between clinical and morphologic findings in unstable angina.

This study was undertaken to verify the hypothesis that the discrepant findings in published reports on the prevalence of thrombus in unstable angina depend on the inclusion of different clinical subsets in the various studies. We therefore correlated the clinical characteristics of patients included under the label of unstable angina with the morphologic features assessed by coronary angiography and intravascular ultrasound, and with histopathologic findings of atherectomy specimens. Fifty-eight patients with unstable angina (class B of the Braunwald classification) undergoing coronary arteriography followed by either coronary angioplasty (n = 20) or directional coronary atherectomy (n = 38) were studied. Fifteen patients were in class IB and 43 were in class II to IIIB. Among these 43 patients with angina at rest, 28 had ST-segment elevation during pain, and 15 had ST-segment depression, and 26 developed negative T waves on the baseline electrocardiogram (ECG) as a result of prolonged or repeated episodes of resting chest pain. Intravascular ultrasound examination of the culprit lesion was performed in 43 patients before the interventional procedure, and histopathologic analysis of atherectomy specimens was performed in 38 patients. Complex lesion morphology by angiography was observed in 31 patients (53%) without any significant relation to various clinical subsets. Patients in Braunwald class IB had more calcific plaques than patients in class II to IIIB (p < 0.001). Among patients with angina at rest, those with negative T waves on the baseline ECG, as well as those with transient ST elevation during pain, had a significantly higher incidence of noncalcific lesions (p = 0.001 for both). Analysis of atherectomy specimens revealed acute coronary lesions (thrombus and/or intraplaque hemorrhage) in 18 patients (47%). The incidence of acute coronary lesions was significantly higher in patients with than without negative T waves on the baseline ECG (p = 0.005), and increased further when negative T waves were combined with ST elevation during pain (p = 0.001). Multivariate analysis revealed that the presence orf negative T waves on the baseline ECG was the only explanatory variable related to the presence of acute coronary lesions by histology (p = 0.03). Patient subsets included in the broad spectrum of unstable angina have different morphologic features and incidence of acute coronary lesions by histology. These data provide an explanation for the discrepant findings in published reports on the relevance of thrombus formation in the pathogenesis of unstable angina.

Angina, Unstable↗

Comparison of dobutamine stress echocardiography with dipyridamole stress echocardiography for detection of viable myocardium after myocardial infarction treated with thrombolysis.

OBJECTIVE: To compare the ability of dobutamine and dipyridamole stress echocardiography to detect functional recovery of stunned but viable myocardial regions early after acute myocardial infarction, and to predict late functional recovery of the reperfusion salvaged myocardium within the infarct area. METHODS: Within 10 d of acute myocardial infarction, 51 patients--30 anterior and 21 inferior, 44 Q wave and seven non-Q-wave infarction--were submitted to a dobutamine echocardiography test at low dose (5-10 micrograms/kg/min over 5 min) and high dose (20-40 micrograms/kg/min over 3 min) and to dipyridamole echocardiography test (0.56 mg/kg over 4 min + 0.28 mg/kg over 2 min) on different days and in random order, after interruption of any vasoactive drug. Resting echocardiography was repeated at two months in 41 of 51 patients (80%). Regional wall motion of the left ventricle was analysed in a semiquantitative manner on a 14-segment model. Viability was defined as improvement of one grade or more of at least two basally asynergic segments in the infarcted area. RESULTS: Regional functional recovery was detected by low dose dobutamine in 38/51 patients (75%) and in 147/308 (48%) of basally asynergic segments, compared to 25/51 patients (49%; P < 0.001) and 78/308 segments (25%; P < 0.001) only identified by dipyridamole. Late spontaneous functional recovery was detected in 24/41 patients (59%) and in 78/254 basally asynergic segments (31%). The sensitivity of dobutamine and dipyridamole echocardiography for predicting spontaneous functional recovery was 72% and 51% respectively (P < 0.001), specificity 68% and 82% (P < 0.001), positive predictive value 50% and 56%, and negative predictive value 85% and 79%. CONCLUSIONS: In comparison with dipyridamole in patients with thrombolysed myocardial infarction, dobutamine induces regional functional recovery. This suggests that dobutamine is more sensitive in showing the presence of viable myocardium within the infarct zone, though it has a lower specificity in predicting delayed spontaneous functional recovery of non-contractile but still viable areas.

Coronary Angiography↗

Outcome of patients with acute myeloid leukemia who failed to respond to a single course of first-line induction therapy: a GIMEMA study of 218 unselected consecutive patients. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

The outcome of a cohort of 218 consecutive patients who failed to respond to a single course of standard daunorubicin plus ARAC (three + seven) induction regimen has been retrospectively evaluated to assess the characteristics of this group of AML patients and the effectiveness of second-line induction programs. Seventy-four of the 218 patients (33.9%) attained complete remission with salvage chemotherapies. The multivariate analysis of pretherapy characteristics of the patients showed that peroxidase positivity and age were the most important factors in determining whether or not the patient would have a favorable response to second-line induction regimen. In addition, comparison of marrow characteristics at diagnosis with those of marrow after the first-line therapy (marrow leukemic index, MLI) provided the greatest differences between second-line CR and resistant patients. Finally, peroxidase positivity and MLI predicted for remission duration and overall survival. Allogeneic BMT, however, appeared the most important factor for survival and event-free survival of remitting patients. These results are of importance when considering that better defined prognostic factors provide an objective rationale for selecting appropriate strategies for the treatment of patients who do not respond to a single course of induction regimen.

Acute Disease↗

[Histopathologic features in atherectomy samples obtained from patient with unstable angina, stable angina and restenosis. Directional Atherectomy Lombardi Group].

BACKGROUND: The present study was aimed at investigating the pathologic features of directional coronary atherectomy (DCA) samples obtained from 194 patients (14 females) with stable (n = 68) and unstable (n = 95) angina, and with restenosis (n = 27). METHODS: DCA samples were obtained from culprit lesions, using the Simpson technique. Unstable angina was classified according to E. Braunwald criteria. Stable angina was grouped according to the presence or absence of a prior myocardial infarction (MI). DCA samples were fixed, processed, serially cut and stained with hematoxilin-eosin and with Movat pentachrome stain. RESULTS: The major pathologic findings were thrombosis, inflammation of the superficial plaque layers, and neointimal hyperplasia which often coexisted within a same sample. Their frequencies, in that order, were distributed in the differing groups of patients as follows: 21% (n = 9), 29.2% (n = 12) and 51% (n = 21) of the 41 cases with stable angina without prior MI. 40.7% (n = 11), 40.7% (n = 11), and 51.8% (n = 14) of the 27 cases with stable angina with prior MI. 25% (n = 4), 56.2% (n = 9) and 68.7% (n = 11), of the 16 cases with BI unstable angina. 35.3% (n = 14), 55.8% (n = 19) and 44% (n = 15), of the 34 cases with BII unstable angina. 44.4% (n = 4), 33.3% (n = 3) and 33.3% (n = 3), of the 9 cases with BIII unstable angina. 48.2% (n = 14), 48.2% (n = 14) and 51.8% (n = 15), of the 29 cases with CII unstable angina at 35.8 days after MI. 60% (n = 3), 60% (n = 3) and 40% (n = 2), of the 5 cases with CIII unstable angina at 8.3 days after MI. 26% (n = 7), 48% (n = 13) and 85.1% (n = 23), of the 27 cases with restenosis. According to above observation, the frequency of coronary thrombosis increases with the increase of the severity of myocardial ischemia. However, thrombosis is not found in most unstable angina without prior MI (63% of BI-II-III unstable angina cases do not have thrombus). In addition, thrombus is not a specific finding of unstable angina, given its occurrence, although in a much lower percentage of cases, in stable angina and in restenosis. CONCLUSIONS: Present data show that different ischemic and plaque lesions. This observation questions on the pathogenetic role of thrombus in unstable angina and calls for further investigations on inflammation and neointimal hyperplasia, as well as on the the reciprocal relation between these findings which are often combined within a same lesion.

Adult↗

Clinical and angiographic correlates of leukocyte activation in unstable angina.

OBJECTIVES: This study sought to evaluate the relation, if any, between clinical and angiographic findings in patients with unstable angina and monocyte and neutrophil CD11b/CD18 receptor density. The expression of HLA-DR molecules on T lymphocytes, an index of activation of these cells, was also investigated. BACKGROUND: Although activation of neutrophils and monocytes has recently been shown in unstable angina, no studies have correlated activation indexes with clinical and angiographic features of patients with this clinical condition. METHODS: Sixty patients underwent diagnostic coronary arteriography and simultaneous blood sampling from the aorta and coronary sinus before injection of contrast medium. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytometry using monoclonal antibodies tagged with fluorescent markers. RESULTS: In 38 patients with unstable angina, neutrophils and monocytes showed a significantly higher expression of CD11b/CD18 adhesion receptors in coronary sinus than aortic blood (p < 0.0001 and p < 0.001, respectively). When these patients were analyzed according to clinical characteristics or angiographic findings, no difference in CD11b/CD18 receptor expression in coronary sinus blood was found between the various subgroups, except for patients with at least one episode of chest pain at rest within 48 h of coronary arteriography and a higher neutrophil adhesion molecule density than patients who remained asymptomatic (p = 0.04). Lymphocytes in patients with stable and unstable angina showed a similar percent expression of CD2/CD19 and CD3/HLA-DR antigens, with no difference between aortic and coronary sinus blood. CONCLUSION: These results in a larger cohort confirm previous data that neutrophil and monocyte CD11b/CD18 adhesion molecules show a higher expression in the coronary sinus blood of patients with unstable angina. Among clinical and angiographic findings in patients with unstable angina, only the occurrence of chest pain within 48 h of coronary angiography was related to significantly higher values of neutrophil fluorescence intensity, suggesting that the degree of neutrophil activation is related to the proximity of rest angina episodes to blood sampling. Finally, our data do not support the concept of systemic or transcardiac lymphocyte activation in unstable angina.

Adult↗

Comparison of coronary lesions obtained by directional coronary atherectomy in unstable angina, stable angina, and restenosis after either atherectomy or angioplasty.

The present study investigated the incidence of the histopathologic lesions and of growth factor expression in a consecutive series of directional coronary atherectomy (DCA) samples from 40 unstable angina pectoris patients without prior acute myocardial infarction and compared the findings with those obtained in DCA samples from 18 patients with stable angina without previous infarction and 18 patients with restenosis. We investigated coronary thrombosis, neointimal hyperplasia, and inflammation. For unstable angina, we correlated the angiographic Ambrose plaque subtypes with the histopathologic findings. The immunophenotype of plaque cells and the growth factor expression were assessed with specific antibodies for cell characterization and for the expression of basic fibroblast and platelet-derived AA and AB growth factors and receptors. The incidence of coronary thrombosis was 35% in patients with unstable angina, 17% in those with stable angina, and 11% in patients with restenosis. Neointimal hyperplasia was found in 38% of unstable angina cases, in 17% of stable angina cases, and in 83% of restenosis cases. Inflammation without thrombus or accelerated progression occurred in 20% of unstable angina and 6% of stable angina samples. In 52% of unstable angina cases, inflammation coexisted with thrombosis and/or neointimal hyperplasia. In the unstable angina group, 71% of the plaques with thrombus had a corresponding angiographic pattern of complicated lesions. The growth factor expression, reported as percentage of cells immunostaining with different growth factor antibodies, was highest in restenosis, followed by unstable angina and stable angina lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of plaque composition on luminal gain after balloon angioplasty, directional atherectomy, and coronary stenting.

This study was conducted to correlate the acute luminal enlargement achieved by three different nonsurgical revascularization procedures in 79 patients (32 treated by balloon angioplasty, 29 by directional atherectomy, and 18 by coronary stenting) with the morphologic characteristics of coronary plaques assessed by preprocedure intravascular ultrasound. The absolute luminal gain was 2.41 +/- 1.54 mm2 for balloon angioplasty, 3.17 +/- 1.8 mm2 for directional atherectomy, and 4.56 +/- 1.45 mm2 for coronary stenting (p = 0.00005). However, when luminal gain was corrected for the external vessel area (luminal gain index), such difference was no longer present (0.22 +/- 0.12 for balloon angioplasty, 0.24 +/- 0.15 for directional atherectomy, and 0.30 +/- 0.12 for coronary stenting, p = not significant). Concentric plaques treated by coronary stenting had a higher luminal gain index than eccentric plaques (p = 0.01). A comparison of the three devices showed that a similar luminal gain index was achieved in soft plaques, whereas coronary stenting was superior to directional atherectomy (0.41 +/- 0.10 vs 0.20 +/- 0.09, p = 0.002) and balloon angioplasty (0.41 +/- 0.10 vs 0.19 +/- 0.08, p = 0.0005) in concentric plaques. Coronary stenting also induced a greater luminal gain index than directional atherectomy in calcific plaques (0.30 +/- 0.11 vs 0.18 +/- 0.09, p = 0.04). In conclusion, these data show that plaque morphology assessed by preprocedure intracoronary ultrasound influences the acute luminal enlargement achieved by different coronary interventions. The knowledge of plaque composition may be useful in guiding the choice of the device to be used to obtain a larger acute luminal gain.

Adult↗