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Biomedical subjects

G Specchia

Publications and source records attributed to G Specchia.

At least 109 records · Page 6Linked to original sources
PubMed1994

Acute promyelocytic leukemia: morphological aspects.

Among AML with maturation, acute promyelocytic leukemia (APL) represents a distinct subtype which accounts for 5-10% of all the FAB variants. APL may be recognized by different cytological pictures: (i) Hypergranular APL, the most typical form, showing promyelocytes with cytoplasm packed with purple granules. Most of the primary granules may be incorporated into Auer rods, sometimes stacked in bundles of faggots. (ii) Microgranular APL, characterized by fine dustlike granulation in the cytoplasm; some promyelocytes may even appear agranular by light microscopy. Most of the cells show bilobed or folded nuclei, a picture which may simulate that of acute myelomonocytic leukemia. (iii) Hyperbasophilic form, characterized by cells with high N/C ratio, and strongly basophilic cytoplasm with either sparse or no granules. Conspicuous cytoplasmatic budding is usually present, recalling the feature of micromegakaryocytes. Strong positivity for myeloperoxidase, Sudan black B and chloroacetate esterase represents the typical cytochemical pattern of M3; usually a weaker reactivity may be observed in M3v. However, sometimes a degree of cytochemical heterogeneity of APL cells may be observed, as suggested by cases displaying a strong sodium fluoride-sensitive non-specific esterase reaction. Recently a distinct entity associated with basophilic differentiation has been described. Differential diagnosis of this form with M2-baso subtype and with cases of MDS or AML with basophilia (M2, M4 with t(6;9) translocation) may be obtained by the use of cytochemistry, cytogenetic investigations, and electron microscopy.

Basophils↗
PubMed1994

[Coronary vasomotor response to acetylcholine correlates with plasma levels of cyclosporin and triglycerides in patients with heart transplantation].

BACKGROUND: Vasoconstriction of normal coronary arteries has been reported after intracoronary (i.c.) administration of acetylcholine (Ach) in cardiac transplant patients and has been related to early endothelial disfunction; the clinical correlates of this response are still unknown. METHODS: We infused graded i.c. concentrations of Ach in 32 pts with angiographically smooth coronary arteries 1 to 3 years after heart transplantation. Changes in diameters of the proximal and middle segments of the left anterior descending coronary artery were measured by quantitative coronary angiography (automatic edge detection). RESULTS: The response to Ach ranged from +44% to -58%; at linear regression analysis it was significantly related to the plasma levels of cyclosporine (r = -0.39, p < .05) and triglycerides (r = -0.42, p < .02) but not to vessel diameter, recipient and donor age, time after transplantation, hypertension, cholesterol levels, number of acute rejection episodes and previous cytomegalovirus infections. CONCLUSIONS: In heart transplant pts with angiographically normal coronary arteries i.c. Ach may reveal endothelial disfunction which is associated with high cyclosporine and triglycerides plasma levels. Whether this response may predict an earlier development of coronary disease remains to be elucidated.

Acetylcholine↗
PubMed1993

Assessment of left ventricular function by isometric handgrip exercise after thrombolysis in patients with refractory unstable angina.

The handgrip test has been proposed for the evaluation of the hemodynamic reserve in patients with coronary artery disease and to quantitate the impairment of left ventricular (LV) function. The present study was designed to evaluate the effect of thrombolytic therapy in patients with refractory unstable angina in order to test the hypothesis that a reduction in intracoronary thrombosis could ameliorate their hemodynamic response to the handgrip test. During left heart catheterization, 20 patients with refractory unstable angina of recent onset performed a handgrip test before (HG1) and 24-72 hours after (HG2) being randomized to receive recombinant tissue-type plasminogen activator or placebo, according to a double-blind parallel group design. HG1 induced an increase in heart rate (p < 0.001), in systolic pressure (p < 0.001), and a reduction in ejection fraction (p < 0.05). Changes in LV end-diastolic pressure during baseline handgrip were highly different in individual patients, resulting in a trend toward an increase. Similarly, a different individual response was observed in the behavior of the isovolumetric and relaxation indices. In comparison with HG1, no difference was detected during HG2 in the 2 treatment groups with respect to changes in LV volumes, ejection fraction, LV systolic and diastolic pressures, +dP/dt, (dP/dt)/P, -dP/dt, and tau index. In patients with refractory unstable angina of recent onset, the handgrip test performed before and after thrombolysis did not prove to be useful in assessing directional changes of LV performance, mainly because of the different individual response to the baseline handgrip test.

Angina, Unstable↗
PubMed1993

Morphologic changes induced by acetylcholine infusion in normal and atherosclerotic coronary arteries.

Low doses of acetylcholine induce "endothelium-dependent" dilatation in normal coronary arteries and constriction of diseased vessels. This study investigated morphologic changes induced by perfusion of normal and diseased coronary arteries with low and high doses of acetylcholine. Vessels were excised from a series of beating hearts explanted at transplantation for idiopathic dilated cardiomyopathy and coronary artery disease. Coronary arteries from other explanted hearts, perfused with saline solution under similar conditions were taken as controls. Samples were studied using conventional histopathologic and immunohistochemical methods. Coronary arteries were grouped according to presence or absence of histologically detectable structural modifications of any type and extent. Low doses of acetylcholine induced changes in all but 1 structurally diseased coronary artery, whereas no change was induced in any but 1 histologically normal coronary artery. High doses of acetylcholine induced contraction changes in both normal and diseased vessels. Changes observed in the wall of the contracted vessels were: (1) endothelial cell contraction with protruding nuclei and detachment of their intercellular junctions with exposure of subjacent collagen to flow, (2) contraction of plaque smooth muscle cells, (3) formation of cushions protruding into vessel lumens causing blunt microchannels. Contraction in both intimal and plaque cells occurred even in diseased vessel segments with intimal denudation. These effects seemed to be dose-dependent in structurally normal vessels because low doses of acetylcholine did not produce any morphologically detectable changes in histologically normal coronary arteries, while low doses of acetylcholine induced similar reactions in vessels affected by both atherosclerosis and subintimal fibrocellular thickening.

Acetylcholine↗
PubMed1993

Influence of elastic recoil on restenosis after successful coronary angioplasty in unstable angina pectoris.

The elastic behavior of the dilated coronary vessel has been reported to affect the immediate results of coronary angioplasty. To determine whether elastic recoil may also influence the long-term restenosis process, 98 consecutive patients with unstable angina and 1-vessel disease were studied. An automated coronary quantitative program was used for the assessment of balloon and coronary luminal diameters. Elastic recoil was defined as the percent reduction between minimal balloon diameter at the highest inflation pressure and minimal lesion diameter immediately after coronary angioplasty. Follow-up coronary arteriography was performed 8 to 12 months after the procedure in all patients. The mean elastic recoil averaged 17.7 +/- 16% and was correlated to the degree of residual stenosis immediately after coronary angioplasty (r = 0.64; p < 0.001). Restenosis, defined as > 50% diameter stenosis at follow-up, developed in 53 patients (54%). There was no correlation between the degree of elastic recoil and the changes in minimal lesion diameter observed during follow-up, whereas a positive correlation between the amount of elastic recoil and the incidence of restenosis was documented (r = 0.84; p < 0.05). Thus, the elastic properties of the dilated vessel do not influence the active process of restenosis. However, because elastic recoil negatively influences the initial results of angioplasty, it is more likely that further reductions in lumen diameter during follow-up can reach a threshold of obstruction considered critical for a binary definition of restenosis.

Adult↗
PubMed1993

Evidence of a hypercoagulable state in patients with acute lymphoblastic leukemia treated with low dose of E. coli L-asparaginase: a GIMEMA study.

Blood coagulation abnormalities induced by administration of E. coli L-asparaginase were investigated in 25 patients with acute lymphoblastic leukemia treated according to the GIMEMA ALL 0288 trial. Dosage of L-asparaginase was relatively low (6,000 U/m2/day for 7 days total dose 42,000 U/m2) as compared to the conventional dosages (120,000-140,000 U/m2 over 10-14 days). A significant decrease in fibronogen, plasminogen, alpha2-antiplasmin and antithrombin III was observed from day IV of L-asparaginase and it was maximum on day VIII, with return to the baseline levels on day XV. Protein C levels had only a borderline reduction, while no modification of protein S or factor VII was observed. Two of the patients investigated developed thrombosis. The presence of a prothrombotic state induced even by this low dosage of E. coli L-asparaginase was suggested by a significant increase of sensitive markers of hypercoagulability such as fibrinopeptide A, thrombin-antithrombin complexes, and prothrombin fragment F1 + 2.

Adolescent↗
PubMed1993

Cytotoxic activity and mechanism of action of 5-Aza-2'-deoxycytidine in human CML cells.

We investigated the cytotoxic activity and some aspects of the mode of action of 5-aza-2'-deoxycytidine (Aza-dC) in 21 primary cultures of leukemic cells freshly obtained from patients with chronic myeloid leukemia (CML) in blast crisis. The cytotoxic potency of Aza-dC was comparable or even greater than that of 1-beta-D-arabinofuranosylcytosine (Ara-C) in most cases, suggesting that this drug has potential in the therapy of blast crisis of CML. Drug incorporation into DNA was evaluated by exposing leukemic cells simultaneously to 3H-Aza-dC at the concentration of 0.1 micrograms/ml and 14C-thymidine (TdR) used as internal standard. Incorporation of Aza-dC into DNA was detectable in all cases. In 17 samples we evaluated the DNA integrity of leukemic cells exposed to Aza-dC using alkaline elution techniques. The drug caused a detectable amount of DNA alkali labile sites (ALS). DNA-ALS increased in cells exposed to Aza-dC concentrations from 0.1 to 1 microgram/ml but did not further increase at 10 micrograms/ml. A plateau in the levels of DNA-ALS was also seen in human K562 cells exposed to increasing concentrations of Aza-dC from 5 to 10 micrograms/ml, whereas in these cells Aza-dC incorporation into DNA increased with increasing Aza-dC concentrations. Therefore, DNA-ALS caused by Aza-dC are not simply the result of the chemical decomposition of azacytosine molecules incorporated into DNA, but are presumably the result of a saturable DNA repair mechanism (e.g., glycosylases) leading to formation of the apyrimidinic sites.

Antineoplastic Agents↗
PubMed1993

Coronary thrombosis in non-cardiac death.

BACKGROUND: Coronary thrombosis is the major cause of acute myocardial ischaemia but can be, albeit rarely, clinically silent. We investigated a series of autopsy hearts from hospitalized patients who died from non-cardiac causes, to detect and study coronary thrombosis. METHODS: The series consisted of 132 autopsy cases (81 men and 51 women, age range 32-39 years, mean 63 +/- 14), in whom cause of death was confirmed as extracardiac. Major epicardial coronary arteries were isolated from the hearts and routinely processed for histopathological study. We evaluated the presence of coronary atherosclerosis and thrombosis. Plaque size was histologically graded with low magnification lenses. RESULTS: Coronary atherosclerosis, which was found in 110 hearts, caused critical stenosis or occlusion of at least one major vessel in 55 (41.6%) cases. Coronary thrombosis was found in 10 vessels from nine different hearts. One coronary tree presented two thrombi in two different vessels. Thrombi were mural in all but one vessel. We did not observe either deep sub-thrombotic ulceration or atheromatous material mixed with thrombus. Deep thrombus layers often presented organizing features. There was no correlation between thrombosis and degree of vessel stenosis, which was only mildly increased by thrombus. Plaque rupture without thrombus was found in five coronary arteries of five different cases. CONCLUSIONS: Coronary thrombus may overlay the intima of a diseased vessel independently of plaque type and severity. Moreover, thrombosis is more frequent than expected, although it is rare when compared with the spread of coronary atherosclerosis. It may represent a plaque progression mechanism in the natural history of coronary atherosclerosis.

Adult↗
PubMed1993

Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. A case-control study. The PLAT Group.

A case-control comparison within the framework of the prospective, multidisciplinary PLAT Study was performed to assess whether altered baseline fibrinolytic variables were associated with an elevated risk of ischemic thrombotic events in patients with documented coronary, cerebral, and/or peripheral atherosclerotic disease. Fibrinogen, D-dimer, tissue plasminogen activator (t-PA) antigen, and fibrinolytic activity before and after venous stasis (delta = difference between the two values), t-PA inhibitor, and lipid levels in 60 atherosclerotic patients with a thrombotic event during the first year of follow-up were compared with those in 94 atherosclerotic patients without such events, who were matched for age, sex, and diagnosis at enrollment. Events were associated with a higher release of delta t-PA antigen (P = .047), higher D-dimer (P = .024), and higher t-PA inhibitor (P = .001) levels. delta Fibrinolytic activity was correlated inversely with t-PA inhibitor (P < .01) and triglycerides (P < .05). D-Dimer was also correlated with systolic blood pressure (P < .01). Atherosclerotic patients at higher risk of thrombotic ischemic events are characterized by increased fibrin turnover and impaired fibrinolytic activity due to high t-PA inhibitor levels. This hemostatic disequilibrium may participate with conventional risk factors such as elevated triglyceride levels and systolic blood pressure in the multifactorial mechanism of ischemic sequelae in patients with preexisting vascular atherothrombotic disease.

Aged↗
PubMed1993

Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease.

BACKGROUND: A rapid increase in leukocyte adhesion to endothelial cells is one of the first events in the acute inflammatory response and in the pathogenesis of vascular diseases. A subgroup of cell surface glycoproteins (the CD11/CD18 complex) play a major role in the leukocyte adhesion process; in particular, the CD11b/CD18 receptor can be upregulated severalfold in response to chemotactic factors. The purpose of this study was to assess whether upmodulation of granulocyte and monocyte CD11b/CD18 receptors takes place during the passage of blood through the coronary tree of patients with clinical manifestations of ischemic heart disease. METHODS AND RESULTS: Thirty-nine patients who underwent diagnostic coronary arteriography were studied. Group 1 (15 patients) had a clinical diagnosis of unstable angina, group 2 (14 patients) had stable exertional angina, and group 3 (10 patients) had atypical chest pain. Simultaneous sampling from the coronary sinus and aorta was obtained before coronary arteriography. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytofluorimetry using monoclonal antibodies tagged with fluorescent markers. Leukocytes were stained in unseparated blood to avoid in vitro manipulation that could activate phagocytes. Group 1 and 2 patients had significant coronary artery disease (> 50% coronary narrowing in at least one major coronary vessel), whereas group 3 patients had normal coronary arteries. In group 1, granulocytes and monocytes showed a significantly higher expression of the CD11b/CD18 adhesion receptor in the coronary sinus than in the aorta (both P < .01), whereas no difference in CD11b/CD18 expression was seen in groups 2 and 3. CONCLUSIONS: Patients with unstable angina have an increased expression of granulocyte and monocyte CD11b/CD18 adhesion receptors, indicating that an inflammatory reaction takes place within their coronary tree. Activation of these leukocytes may induce coronary vasoconstriction, favor thrombotic processes, and further activate platelets, thus having potential implications on the pathogenesis of unstable coronary artery disease.

Adult↗
PubMed1993

[Coronary angioplasty in unstable angina].

Percutaneous transluminal coronary angioplasty is now largely applied either to stable or unstable patients suffering from angina pectoris. The procedural success rate and the incidence of acute complications are now comparable in the 2 population of patients. Very recent data have also shown that there is no difference in restenosis between patients with stable or unstable angina. Therefore, by now, in such unstable coronary syndromes the choice of surgical therapy is mainly determined by the presence of multivessel disease or by depressed left ventricular function. However, the possibility to obtain a complete revascularization by angioplasty or to stabilize the patients treating only the "culprit" vessel, may increase the number of unstable patients shifting from surgery to angioplasty.

Angina, Unstable↗
PubMed1993

[K-channel activators and cardioprotection].

The hemodynamic effects of K-channel openers suggest that these drugs should be beneficial in the management of hypertension and angina. Many experimental data have also shown that K-channel openers exert effective cardioprotection, decreasing the deleterious consequences of myocardial ischemia and limiting the damage induced by reperfusion. The mechanism of myocardial protection during ischemia is still unclear, even though there are experimental results that suggest that K-channel openers may act in the same way as preconditioning. The reduction of Ca-overload and the inhibitory effect on oxidative damage are possible explanations for the myocardial protection during reperfusion.

Humans↗
PubMed1993

[The evaluation of intracoronary stents by intravascular echography].

BACKGROUND: Intravascular ultrasound (IVUS) provides high resolution of vessel wall pathoanatomy, and because of the highly reflective nature of stent surfaces, can evaluate alterations in stent geometry. METHODS: This study was performed to assess, by IVUS stent, expansion patterns in patients undergoing implantation of metallic coronary stents, and the mechanisms of restenosis in those patients. Twenty-five patients were studied: 9 pts acutely and 16 pts at routine follow-up 5-8 months after Palmaz-Schatz stent placement. The images recorded by IVUS (25 Mhz 3.9F catheter Intertherapy Inc. California) were quantitatively analyzed for: luminal diameter (LD), luminal cross-sectional area (LA), cross-sectional diameter (SD) and area (SA), comprised by the stent struts. We used quantitative coronary angiography (QCA) (Image Comm System) to measure lumen diameter (LD) and luminal cross-sectional area (LA) in patients in whom IVUS was not performed at the moment of stent placement. These values were considered reference values of LD and LA of the stent at follow-up. RESULTS: During follow-up, patients showed a reduction of vessel lumen LD (2.09 +/- 0.17 mm) measured by IVUS, versus baseline LD (2.87 +/- 0.39 mm) measured by QCA. SD (2.76 +/- 0.31 mm) and SA (6.30 +/- 1.24 mm2) were unchanged in comparison with LD (2.87 +/- 0.39 mm) and LA (6.47 +/- 1.77 mm2) measured by QCA at the time of stent implantation. CONCLUSIONS: These data suggest that the mechanism of restenosis is due to intimal proliferation rather than stent collapse.

Angioplasty, Balloon, Coronary↗
PubMed1992

Similar antiischemic effects of intracoronary atenolol and nifedipine during brief coronary occlusions in humans.

To compare the antiischemic effects of intracoronary administration of a beta blocker, atenolol, and of a calcium antagonist, nifedipine, on the clinical and electrocardiographic signs of myocardial ischemia induced by balloon occlusion of the coronary artery, we studied 32 consecutive patients undergoing routine PTCA. In each patient at least three balloon inflations were performed: the first served to verify the occurrence of ischemia (ST segment depression/elevation greater than 1.5 mm); the second was used as a control occlusion; the third was performed after the patients were assigned to receive either atenolol 1.0 mg IC (group 1, N = 16) or nifedipine V = 0.2 mg IC (group 2, N = 16). In a control population of 10 patients, the time to return to baseline of the ECG tended to be progressively shorter during the three consecutive inflations, but the other clinical and ECG parameters did not change significantly. In group 1 and group 2, two patients did not show ECG signs of ischemia at the third inflation; the time to ischemia increased in group 1 (+76%, p less than .001) and group 2 (+85%, p less than .01; NS group 1 versus group 2); ST segment displacement at 30 seconds decreased in group 1 (-38%, p less than .01) and group 2 (-36%, p less than .01; NS group 1 versus group 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Dobutamine-induced ST segment elevation in a patient with angina at rest and critical coronary lesions.

A case of dobutamine-induced ST-segment elevation in a patient with angina at rest and severe two-vessel disease is described. Coronary angiography performed during the ischaemic episode showed patency of coronary arteries; ST-segment elevation and chest pain regressed after propranolol administration. This case suggests that in the presence of severe coronary lesions dobutamine may produce transmural myocardial ischaemia by increasing myocardial oxygen demand and inducing myocardial blood flow maldistribution.

Angina Pectoris↗
PubMed1992

Constitutive expression of IL-1 beta, M-CSF and c-fms during the myeloid blastic phase of chronic myelogenous leukaemia.

During the myeloid blast crisis (BC) of chronic myelogenous leukaemia (CML) non-random additional chromosome abnormalities occur in over 80% of patients. However, these cytogenetic changes have been reported to precede the clinical signs of CML-BC by several months to years suggesting that other biological events may participate in the multistep process of acute transformation of CML. The autocrine production of growth factors has been recently shown to occur in several haematological malignancies and particularly in acute myeloblastic leukaemia (AML). In the present report we demonstrate that IL-1 beta gene is expressed in almost all cases of CML in myeloid blast crisis. The secretion of IL-1 from CML blasts in culture supernatants was confirmed in all five of the patients we studied. A high proportion of cases showed constitutive expression of the M-CSF gene and many of the same patients often had a simultaneous co-expression of the proto-oncogene c-fms which encodes for the M-CSF receptor. After exposure of leukaemic cells to phorbol myristate acetate (PMA), release of M-CSF protein was documented in three of five patients studied. No significant interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF), was detected in these patients demonstrating that a different pattern of growth factors secretion exist in AML and CML, where distinct molecular events are likely involved in the control of leukaemic proliferation.

Adult↗
PubMed1992

Mitoxantrone and continuous infusion of cytosine arabinoside in refractory and relapsed acute lymphoblastic leukemia.

Twenty adult patients with relapsed or refractory acute lymphoblastic leukemias (ALL) received a regimen employing two courses of mitoxantrone 12 mg/m2 by rapid intravenous infusion on days 1, 2 and 3 and cytosine arabinoside (ARA-C) 200 mg/m2/day by continuous infusion on days 1-7. Complete remission (CR) was achieved in 10 of 20 (50%) patients (3 refractory and 7 relapsed). Median duration of CR was 5 months (range 2-9). The treatment was associated with minimal extrahematologic toxicity, with no cardiac toxicity. Our results are nearly in line with therapeutic responses obtained with regimens employing megadose therapy (HD ARA-C). Because of acceptable toxicity, mitoxantrone plus continuous infusion of a standard dose of ARA-C could be considered for relapsed of refractory ALL patients eligible for an intensive therapeutic approach (bone marrow transplantation) after a second CR.

Adolescent↗